rs13447682

Positions:

• chr11-94456882-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_005591.4(MRE11):​c.1501-544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0087 in 152,256 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.0087 (9 hom., cov: 32)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.138

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-94456882-G-A is Benign according to our data. Variant chr11-94456882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 223844.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0087 (1324/152256) while in subpopulation NFE AF= 0.015 (1019/68028). AF 95% confidence interval is 0.0142. There are 9 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1324 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRE11	NM_005591.4	c.1501-544C>T		intron_variant		ENST00000323929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRE11	ENST00000323929.8	c.1501-544C>T		intron_variant		1	NM_005591.4	P3
MRE11	ENST00000323977.7	c.1501-544C>T		intron_variant		1
MRE11	ENST00000393241.8	c.1501-544C>T		intron_variant		5		A1
MRE11	ENST00000407439.7	c.1510-544C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1323 AN: 152138 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00925

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00526

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

GnomAD4 genome AF: 0.00870 AC: 1324 AN: 152256 Hom.: 9 Cov.: 32 AF XY: 0.00783 AC XY: 583 AN XY: 74430

Gnomad4 AFR AF: 0.00272

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00318

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00925

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0119 Hom.: 1

Bravo AF: 0.00821

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, no assertion criteria provided

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Dec 01, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.8
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs13447682; hg19: chr11-94190048;