rs641936

Positions:

chr11-94464094-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005591.4(MRE11):c.1225+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,608,042 control chromosomes in the GnomAD database, including 102,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10427 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91640 hom. )

Consequence

MRE11
NM_005591.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.49

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-94464094-A-G is Benign according to our data. Variant chr11-94464094-A-G is described in ClinVar as [Benign]. Clinvar id is 193884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-94464094-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRE11	NM_005591.4 linkuse as main transcript	c.1225+19T>C		intron_variant		ENST00000323929.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MRE11	ENST00000323929.8 linkuse as main transcript	c.1225+19T>C	intron_variant	1	NM_005591.4	P3	P49959-1
MRE11	ENST00000323977.7 linkuse as main transcript	c.1225+19T>C	intron_variant	1			P49959-2
MRE11	ENST00000393241.8 linkuse as main transcript	c.1225+19T>C	intron_variant	5		A1
MRE11	ENST00000407439.7 linkuse as main transcript	c.1234+19T>C	intron_variant	2			P49959-3

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55979

AN:

151908

Hom.:

10417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.389

GnomAD3 exomes

AF:

0.382

AC:

95495

AN:

250300

Hom.:

18494

AF XY:

0.382

AC XY:

51683

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.387

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.352

AC:

512471

AN:

1456014

Hom.:

91640

Cov.:

AF XY:

0.354

AC XY:

256805

AN XY:

724550

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.368

AC:

56020

AN:

152028

Hom.:

10427

Cov.:

AF XY:

0.374

AC XY:

27762

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.356

Hom.:

1764

Bravo

AF:

0.370

Asia WGS

AF:

0.380

AC:

1322

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ataxia-telangiectasia-like disorder 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Apr 14, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 04, 2016	Variant summary: c.1225+19T>C in MRE11A gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.378 (45400/120008 chrs tested), including numerous homozygous occurrence. The observed frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.006%, suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign/Polymorphism by reputable databases/clinical laboratory and in published reports (Bartkova, 2008). Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Ataxia-telangiectasia-like disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.11

DANN

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over