rs10831227

Variant names:

• chr11-94422411-G-A
• rs10831227
• NM_005591.4:c.2071-2230C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-94422411-G-A
• chr11-94422411-G-C

Variant summary

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

The NM_005591.4(MRE11):​c.2071-2230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,792 control chromosomes in the GnomAD database, including 6,384 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 0.27 (6384 hom., cov: 31)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.2071-2230C>T		intron_variant	Intron 19 of 19	ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.2071-2230C>T		intron_variant	Intron 19 of 19	1	NM_005591.4	ENSP00000325863.4
MRE11	ENST00000323977.7	c.1987-2230C>T		intron_variant	Intron 18 of 18	1		ENSP00000326094.3
MRE11	ENST00000407439.7	c.2080-2230C>T		intron_variant	Intron 19 of 19	2		ENSP00000385614.3
MRE11	ENST00000393241.8	c.2068-2230C>T		intron_variant	Intron 19 of 19	5		ENSP00000376933.4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41517 AN: 151676 Hom.: 6379 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.274 AC: 41549 AN: 151792 Hom.: 6384 Cov.: 31 AF XY: 0.273 AC XY: 20244 AN XY: 74158

African (AFR) AF: 0.130 AC: 5390 AN: 41386

American (AMR) AF: 0.301 AC: 4597 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1422 AN: 5146

South Asian (SAS) AF: 0.226 AC: 1086 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3470 AN: 10504

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23030 AN: 67906

Other (OTH) AF: 0.287 AC: 605 AN: 2106

Alfa AF: 0.305 Hom.: 946

Bravo AF: 0.268

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.49
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10831227; hg19: chr11-94155577;