chr11-94501415-C-T

Variant names:

• chr11-94501415-C-T
• rs610899
• XM_011542837.3:c.-105-8509G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011542837.3(MRE11):​c.-105-8509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,942 control chromosomes in the GnomAD database, including 25,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25748 hom., cov: 32)
• Consequence: MRE11 XM_011542837.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88195 AN: 151822 Hom.: 25721 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 88277 AN: 151942 Hom.: 25748 Cov.: 32 AF XY: 0.578 AC XY: 42943 AN XY: 74254

African (AFR) AF: 0.613 AC: 25378 AN: 41430

American (AMR) AF: 0.506 AC: 7717 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2045 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3086 AN: 5180

South Asian (SAS) AF: 0.451 AC: 2172 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6401 AN: 10544

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39450 AN: 67936

Other (OTH) AF: 0.564 AC: 1189 AN: 2108

Alfa AF: 0.590 Hom.: 3650

Bravo AF: 0.579

Asia WGS AF: 0.542 AC: 1883 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.30
PhyloP100		-0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs610899; hg19: chr11-94234581;