rs496797

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1

The NM_001440471.1(MRE11):c.-56+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,326,302 control chromosomes in the GnomAD database, including 134,746 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20535 hom., cov: 32)

Exomes 𝑓: 0.43 ( 114211 hom. )

Consequence

MRE11
NM_001440471.1 splice_donor, intron

Scores

Splicing: ADA: 0.00009732

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

Publications

24 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 -8 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

BP6

Variant 11-94492641-C-T is Benign according to our data. Variant chr11-94492641-C-T is described in ClinVar as Benign. ClinVar VariationId is 1256637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440471.1. 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.20+141G>A	intron	N/A	NP_005582.1	P49959-1
MRE11	NM_001440460.1		c.20+141G>A	intron	N/A	NP_001427389.1
MRE11	NM_001440461.1		c.20+141G>A	intron	N/A	NP_001427390.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRE11	ENST00000323929.8	TSL:1 MANE Select	c.20+141G>A	intron	N/A	ENSP00000325863.4	P49959-1
MRE11	ENST00000323977.7	TSL:1	c.20+141G>A	intron	N/A	ENSP00000326094.3	P49959-2
MRE11	ENST00000540013.5	TSL:1	c.20+141G>A	intron	N/A	ENSP00000440986.1	F5GXT0

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77839

AN:

151936

Hom.:

20515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.517

GnomAD2 exomes

AF:

0.497

AC:

85441

AN:

171858

AF XY:

0.498

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.550

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.435

AC:

510302

AN:

1174248

Hom.:

114211

Cov.:

AF XY:

0.442

AC XY:

261299

AN XY:

590846

show subpopulations

African (AFR)

AF:

0.628

AC:

16533

AN:

26338

American (AMR)

AF:

0.545

AC:

19914

AN:

36514

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

10858

AN:

23842

East Asian (EAS)

AF:

0.524

AC:

19048

AN:

36376

South Asian (SAS)

AF:

0.605

AC:

45628

AN:

75402

European-Finnish (FIN)

AF:

0.453

AC:

20900

AN:

46112

Middle Eastern (MID)

AF:

0.535

AC:

2494

AN:

4660

European-Non Finnish (NFE)

AF:

0.403

AC:

352228

AN:

874870

Other (OTH)

AF:

0.453

AC:

22699

AN:

50134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

12880

25759

38639

51518

64398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9884

19768

29652

39536

49420

<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:

0.512

AC:

77907

AN:

152054

Hom.:

20535

Cov.:

AF XY:

0.517

AC XY:

38387

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.634

AC:

26314

AN:

41474

American (AMR)

AF:

0.537

AC:

8209

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1531

AN:

3470

East Asian (EAS)

AF:

0.491

AC:

2542

AN:

5176

South Asian (SAS)

AF:

0.604

AC:

2909

AN:

4814

European-Finnish (FIN)

AF:

0.466

AC:

4921

AN:

10560

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.442

AC:

30023

AN:

67948

Other (OTH)

AF:

0.510

AC:

1080

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1946

3892

5839

7785

9731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.501

Hom.:

7756

Bravo

AF:

0.519

TwinsUK

AF:

0.421

AC:

1562

ALSPAC

AF:

0.435

AC:

1678

ExAC

AF:

0.418

AC:

47298

Asia WGS

AF:

0.533

AC:

1851

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.34

(source)

DANN

Benign

0.84

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0032

PhyloP100

-1.3

GERP RS

-0.0015

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000097

dbscSNV1_RF

Benign

0.0040

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