11-94445959-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005591.4(MRE11):c.1784-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,106,224 control chromosomes in the GnomAD database, including 123,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17884 hom., cov: 33)
  • Exomes 𝑓: 0.46 (105340 hom.)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.676

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-94445959-T-C is Benign according to our data. Variant chr11-94445959-T-C is described in ClinVar as [Benign]. Clinvar id is 1264255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRE11	NM_005591.4	c.1784-66A>G		intron_variant		ENST00000323929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRE11	ENST00000323929.8	c.1784-66A>G		intron_variant		1	NM_005591.4	P3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73191 AN: 151932 Hom.: 17864 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.462 AC: 440372 AN: 954174 Hom.: 105340 AF XY: 0.468 AC XY: 232080 AN XY: 495914

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.532

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.482 AC: 73256 AN: 152050 Hom.: 17884 Cov.: 33 AF XY: 0.487 AC XY: 36225 AN XY: 74322

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.491

Alfa AF: 0.447 Hom.: 2479

Bravo AF: 0.483

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.6
Dann	Benign	0.67

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: rs1014666; hg19: chr11-94179125; COSMIC: COSV60574018;