Genetic Variant MRE11:c.*2466T>C (chr11-94417659-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005591.4(MRE11):c.*2466T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 233,098 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 1 hom. )

Consequence

MRE11
NM_005591.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.621

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-94417659-A-G is Benign according to our data. Variant chr11-94417659-A-G is described in ClinVar as Benign. ClinVar VariationId is 883390.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0058 (884/152352) while in subpopulation AFR AF = 0.0193 (803/41592). AF 95% confidence interval is 0.0182. There are 14 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRE11	NM_005591.4	MANE Select	c.*2466T>C	3_prime_UTR	Exon 20 of 20	NP_005582.1	P49959-1
MRE11	NM_001440460.1		c.*2466T>C	3_prime_UTR	Exon 21 of 21	NP_001427389.1
MRE11	NM_001440461.1		c.*2466T>C	3_prime_UTR	Exon 21 of 21	NP_001427390.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRE11	ENST00000323929.8	TSL:1 MANE Select	c.*2466T>C	3_prime_UTR	Exon 20 of 20	ENSP00000325863.4	P49959-1
MRE11	ENST00000856310.1		c.*2466T>C	3_prime_UTR	Exon 20 of 20	ENSP00000526369.1
MRE11	ENST00000856311.1		c.*2466T>C	3_prime_UTR	Exon 20 of 20	ENSP00000526370.1

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

879

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0192

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00848

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.00177

AC:

143

AN:

80746

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

AN XY:

37112

show subpopulations

African (AFR)

AF:

0.0211

AC:

AN:

3892

American (AMR)

AF:

0.00121

AC:

AN:

2488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5122

East Asian (EAS)

AF:

0.00265

AC:

AN:

11328

South Asian (SAS)

AF:

0.00

AC:

AN:

700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

494

European-Non Finnish (NFE)

AF:

0.0000200

AC:

AN:

49916

Other (OTH)

AF:

0.00400

AC:

AN:

6748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00580

AC:

884

AN:

152352

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0193

AC:

803

AN:

41592

American (AMR)

AF:

0.00144

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00811

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00328

Hom.:

Bravo

AF:

0.00676

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ataxia-telangiectasia-like disorder 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.86

(source)

DANN

Benign

0.42

PhyloP100

-0.62

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over