11-94492754-C-T

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.20+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,610,794 control chromosomes in the GnomAD database, including 159,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14247 hom., cov: 31)

Exomes 𝑓: 0.44 ( 145456 hom. )

Consequence

MRE11
NM_005591.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.320

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: 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=-0.83).

BP6

Variant 11-94492754-C-T is Benign according to our data. Variant chr11-94492754-C-T is described in ClinVar as Benign. ClinVar VariationId is 259798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4 link	c.20+28G>A		intron_variant	Intron 2 of 19	ENST00000323929.8	NP_005582.1	P49959-1A0A024R395

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8 link	c.20+28G>A		intron_variant	Intron 2 of 19	1	NM_005591.4	ENSP00000325863.4		P49959-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65199

AN:

151734

Hom.:

14242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.449

GnomAD2 exomes

AF:

0.468

AC:

117655

AN:

251248

AF XY:

0.471

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.540

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.443

AC:

646824

AN:

1458942

Hom.:

145456

Cov.:

AF XY:

0.448

AC XY:

324958

AN XY:

725944

show subpopulations

African (AFR)

AF:

0.375

AC:

12528

AN:

33438

American (AMR)

AF:

0.534

AC:

23863

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

11402

AN:

26110

East Asian (EAS)

AF:

0.528

AC:

20934

AN:

39672

South Asian (SAS)

AF:

0.570

AC:

49089

AN:

86192

European-Finnish (FIN)

AF:

0.458

AC:

24439

AN:

53390

Middle Eastern (MID)

AF:

0.483

AC:

2770

AN:

5738

European-Non Finnish (NFE)

AF:

0.428

AC:

475091

AN:

1109402

Other (OTH)

AF:

0.443

AC:

26708

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

18311

36622

54934

73245

91556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14540

29080

43620

58160

72700

<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:

0.430

AC:

65239

AN:

151852

Hom.:

14247

Cov.:

AF XY:

0.436

AC XY:

32364

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.372

AC:

15361

AN:

41342

American (AMR)

AF:

0.504

AC:

7690

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1437

AN:

3462

East Asian (EAS)

AF:

0.491

AC:

2539

AN:

5166

South Asian (SAS)

AF:

0.567

AC:

2730

AN:

4818

European-Finnish (FIN)

AF:

0.465

AC:

4908

AN:

10548

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29279

AN:

67944

Other (OTH)

AF:

0.443

AC:

933

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1883

3766

5650

7533

9416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.438

Hom.:

19858

Bravo

AF:

0.426

Asia WGS

AF:

0.504

AC:

1753

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

-0.83

CADD

Benign

6.5

(source)

DANN

Benign

0.76

PhyloP100

0.32

Mutation Taster

=297/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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