rs370397034

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_005591.4(MRE11):c.1476C>T(p.Ala492Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MRE11
NM_005591.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.229

Publications

0 publications found

Variant links:

Genes affected

MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MRE11 Gene-Disease associations (from GenCC):

ataxia-telangiectasia-like disorder 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
prostate cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

MRE11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-94459432-G-A is Benign according to our data. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94459432-G-A is described in CliVar as Likely_benign. Clinvar id is 185720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.229 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4 link	c.1476C>T	p.Ala492Ala	synonymous_variant	Exon 13 of 20	ENST00000323929.8	NP_005582.1	P49959-1A0A024R395

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRE11	ENST00000323929.8 link	c.1476C>T	p.Ala492Ala	synonymous_variant	Exon 13 of 20	1	NM_005591.4	ENSP00000325863.4	P49959-1
MRE11	ENST00000323977.7 link	c.1476C>T	p.Ala492Ala	synonymous_variant	Exon 13 of 19	1		ENSP00000326094.3	P49959-2
MRE11	ENST00000407439.7 link	c.1485C>T	p.Ala495Ala	synonymous_variant	Exon 13 of 20	2		ENSP00000385614.3	P49959-3
MRE11	ENST00000393241.8 link	c.1476C>T	p.Ala492Ala	synonymous_variant	Exon 13 of 20	5		ENSP00000376933.4	F8W7U8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251392

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111878

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 20, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MRE11: BP4, BP7 -

Hereditary cancer-predisposing syndrome

Benign:1

Jul 29, 2014

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Ataxia-telangiectasia-like disorder

Benign:1

Jan 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.1

(source)

DANN

Benign

0.43

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over