rs16920467

chr11-94454760-A-T

Variant summary

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

The NM_005591.4(MRE11):c.1563+1516T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 152,206 control chromosomes in the GnomAD database, including 323 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 0.056 (323 hom., cov: 31)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRE11	NM_005591.4	c.1563+1516T>A		intron_variant		ENST00000323929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRE11	ENST00000323929.8	c.1563+1516T>A		intron_variant		1	NM_005591.4	P3
MRE11	ENST00000323977.7	c.1563+1516T>A		intron_variant		1
MRE11	ENST00000393241.8	c.1563+1516T>A		intron_variant		5		A1
MRE11	ENST00000407439.7	c.1572+1516T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8548 AN: 152086 Hom.: 324 Cov.: 31

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0593

Gnomad EAS AF: 0.0753

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0562 AC: 8547 AN: 152206 Hom.: 323 Cov.: 31 AF XY: 0.0590 AC XY: 4391 AN XY: 74416

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0593

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0529 Hom.: 33

Bravo AF: 0.0566

Asia WGS AF: 0.0740 AC: 257 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.84

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: rs16920467; hg19: chr11-94187926;