dbSNP rs680695: MRE11:c.403-112T>C (chr11-94478988-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_005591.4(MRE11):c.403-112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,179,136 control chromosomes in the GnomAD database, including 54,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6998 hom., cov: 33)

Exomes 𝑓: 0.30 ( 47433 hom. )

Consequence

MRE11
NM_005591.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.549

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=-0.82).

BP6

Variant 11-94478988-A-G is Benign according to our data. Variant chr11-94478988-A-G is described in ClinVar as [Benign]. Clinvar id is 1222812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4 link	c.403-112T>C		intron_variant	Intron 5 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.403-112T>C		intron_variant	Intron 5 of 19	1	NM_005591.4	ENSP00000325863.4		P49959-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44920

AN:

152018

Hom.:

7000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.323

GnomAD4 exome

AF:

0.297

AC:

305106

AN:

1027000

Hom.:

47433

AF XY:

0.300

AC XY:

156862

AN XY:

523082

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.345

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.295

AC:

44923

AN:

152136

Hom.:

6998

Cov.:

AF XY:

0.301

AC XY:

22375

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.390

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.368

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.288

Hom.:

806

Bravo

AF:

0.294

Asia WGS

AF:

0.339

AC:

1177

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

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

-0.82

CADD

Benign

DANN

Benign

0.51

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