rs1009455

Positions:

• chr11-94491108-C-G

Variant summary

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

The ENST00000323929.8(MRE11):​c.21-143G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 623,782 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (178 hom., cov: 32)
  • Exomes 𝑓: 0.016 (166 hom.)
• Consequence: MRE11 ENST00000323929.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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=-0.87).
• BP6: Variant 11-94491108-C-G is Benign according to our data. Variant chr11-94491108-C-G is described in ClinVar as [Benign]. Clinvar id is 1286133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRE11	NM_005591.4	c.21-143G>C		intron_variant		ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.21-143G>C		intron_variant		1	NM_005591.4	ENSP00000325863	P3

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4842 AN: 152044 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0163 AC: 7694 AN: 471620 Hom.: 166 AF XY: 0.0178 AC XY: 4436 AN XY: 249888

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0000985

Gnomad4 SAS exome AF: 0.0453

Gnomad4 FIN exome AF: 0.000942

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0230

GnomAD4 genome AF: 0.0318 AC: 4844 AN: 152162 Hom.: 178 Cov.: 32 AF XY: 0.0318 AC XY: 2365 AN XY: 74382

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0235 Hom.: 14

Bravo AF: 0.0354

Asia WGS AF: 0.0190 AC: 66 AN: 3472

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

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.032
DANN	Benign	0.59

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: rs1009455; hg19: chr11-94224274;