11-94501415-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: 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	XM_011542837.3	c.-105-8509G>A		intron_variant	Intron 1 of 19		XP_011541139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;