rs7117042

Variant names:

• chr11-94437809-C-T
• rs7117042
• NM_005591.4:c.1868-574G>A

Variant summary

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

The NM_005591.4(MRE11):​c.1868-574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,088 control chromosomes in the GnomAD database, including 1,166 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 0.12 (1166 hom., cov: 33)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.1868-574G>A		intron_variant	Intron 16 of 19	ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.1868-574G>A		intron_variant	Intron 16 of 19	1	NM_005591.4	ENSP00000325863.4
MRE11	ENST00000323977.7	c.1784-574G>A		intron_variant	Intron 15 of 18	1		ENSP00000326094.3
MRE11	ENST00000407439.7	c.1877-574G>A		intron_variant	Intron 16 of 19	2		ENSP00000385614.3
MRE11	ENST00000393241.8	c.1865-574G>A		intron_variant	Intron 16 of 19	5		ENSP00000376933.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17869 AN: 151970 Hom.: 1163 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.118 AC: 17903 AN: 152088 Hom.: 1166 Cov.: 33 AF XY: 0.118 AC XY: 8800 AN XY: 74360

African (AFR) AF: 0.166 AC: 6893 AN: 41490

American (AMR) AF: 0.108 AC: 1654 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.0908 AC: 469 AN: 5164

South Asian (SAS) AF: 0.184 AC: 889 AN: 4826

European-Finnish (FIN) AF: 0.0673 AC: 713 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0990 AC: 6729 AN: 67964

Other (OTH) AF: 0.109 AC: 231 AN: 2110

Alfa AF: 0.110 Hom.: 143

Bravo AF: 0.119

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.83
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7117042; hg19: chr11-94170975;