11-94467796-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005591.4(MRE11):c.1098+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,582,754 control chromosomes in the GnomAD database, including 1,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 431 hom., cov: 32)

Exomes 𝑓: 0.016 ( 641 hom. )

Consequence

MRE11
NM_005591.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.120

Publications

9 publications found

Variant links:

COSMIC-nc: COSV60574296

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-94467796-A-G is Benign according to our data. Variant chr11-94467796-A-G is described in ClinVar as Benign. ClinVar VariationId is 140776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4 link	c.1098+17T>C		intron_variant	Intron 10 of 19	ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MRE11	ENST00000323929.8 link	c.1098+17T>C	intron_variant	Intron 10 of 19	1	NM_005591.4	ENSP00000325863.4
MRE11	ENST00000323977.7 link	c.1098+17T>C	intron_variant	Intron 10 of 18	1		ENSP00000326094.3
MRE11	ENST00000407439.7 link	c.1107+17T>C	intron_variant	Intron 10 of 19	2		ENSP00000385614.3
MRE11	ENST00000393241.8 link	c.1098+17T>C	intron_variant	Intron 10 of 19	5		ENSP00000376933.4

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7254

AN:

152098

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0507

GnomAD2 exomes

AF:

0.0242

AC:

6072

AN:

251188

AF XY:

0.0241

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

AF:

0.0156

AC:

22306

AN:

1430538

Hom.:

641

Cov.:

AF XY:

0.0164

AC XY:

11674

AN XY:

713726

show subpopulations

African (AFR)

AF:

0.149

AC:

4877

AN:

32756

American (AMR)

AF:

0.0157

AC:

702

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0330

AC:

858

AN:

25964

East Asian (EAS)

AF:

0.000177

AC:

AN:

39508

South Asian (SAS)

AF:

0.0449

AC:

3843

AN:

85534

European-Finnish (FIN)

AF:

0.000956

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.0731

AC:

374

AN:

5114

European-Non Finnish (NFE)

AF:

0.00926

AC:

10042

AN:

1084292

Other (OTH)

AF:

0.0262

AC:

1552

AN:

59310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1130

2261

3391

4522

5652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.0477

AC:

7258

AN:

152216

Hom.:

431

Cov.:

AF XY:

0.0465

AC XY:

3464

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.139

AC:

5763

AN:

41492

American (AMR)

AF:

0.0225

AC:

344

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

114

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

737

AN:

68022

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

326

653

979

1306

1632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0173

Hom.:

Bravo

AF:

0.0535

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2016

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The c.1098+17T>C variant affects a non-conserved intronic nucleotide at a position not widely known to affect normal splicing. MutationTaster predicts benign outcome for this variant. 5/5 splice-tools in Alamut predict that this variant does not affect normal splicing. This variant is found in 3285/120390 control chromosomes from ExAC (including 139 homozygotes) at a frequency of 0.0272863, which is about 437 times greater than the maximal expected frequency of a pathogenic allele (0.0000625), suggesting this variant is a benign common polymorphism. Taken together, this variant has been classified as Benign.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ataxia-telangiectasia-like disorder 1

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 08, 2016

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Hereditary cancer-predisposing syndrome

Benign:2

Sep 25, 2012

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: 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.

Jul 10, 2025

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ataxia-telangiectasia-like disorder

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance: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

-0.80

CADD

Benign

2.1

(source)

DANN

Benign

0.41

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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