rs557148

Positions:

• chr11-94481673-T-C
• chr11-94481673-T-G

Variant summary

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

The NM_005591.4(MRE11):​c.315-1912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,066 control chromosomes in the GnomAD database, including 20,771 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 0.51 (20771 hom., cov: 32)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRE11	NM_005591.4	c.315-1912A>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.315-1912A>G		intron_variant		1	NM_005591.4	ENSP00000325863	P3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77373 AN: 151948 Hom.: 20744 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.509 AC: 77451 AN: 152066 Hom.: 20771 Cov.: 32 AF XY: 0.513 AC XY: 38112 AN XY: 74332

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.509

Alfa AF: 0.381 Hom.: 1968

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.41

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: rs557148; hg19: chr11-94214839;