11-94425717-T-C

Position:

• chr11-94425717-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000323929.8(MRE11):​c.2070+4194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,002 control chromosomes in the GnomAD database, including 13,407 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 0.41 (13407 hom., cov: 32)
• Consequence: MRE11 ENST00000323929.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRE11	NM_005591.4	c.2070+4194A>G		intron_variant		ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.2070+4194A>G		intron_variant		1	NM_005591.4	ENSP00000325863	P3
MRE11	ENST00000323977.7	c.1986+4194A>G		intron_variant		1		ENSP00000326094
MRE11	ENST00000393241.8	c.2067+4194A>G		intron_variant		5		ENSP00000376933	A1
MRE11	ENST00000407439.7	c.2079+4194A>G		intron_variant		2		ENSP00000385614

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62954 AN: 151884 Hom.: 13384 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.415 AC: 63022 AN: 152002 Hom.: 13407 Cov.: 32 AF XY: 0.418 AC XY: 31052 AN XY: 74308

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.426

Alfa AF: 0.376 Hom.: 1518

Bravo AF: 0.415

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.27

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: rs541472; hg19: chr11-94158883;