rs16920467

Variant names:

• chr11-94454760-A-T
• rs16920467
• NM_005591.4:c.1563+1516T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

MRE11 Gene-Disease associations (from GenCC):

• ataxia-telangiectasia-like disorder 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• prostate cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.1563+1516T>A		intron_variant	Intron 14 of 19	ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.1563+1516T>A		intron_variant	Intron 14 of 19	1	NM_005591.4	ENSP00000325863.4
MRE11	ENST00000323977.7	c.1563+1516T>A		intron_variant	Intron 14 of 18	1		ENSP00000326094.3
MRE11	ENST00000407439.7	c.1572+1516T>A		intron_variant	Intron 14 of 19	2		ENSP00000385614.3
MRE11	ENST00000393241.8	c.1563+1516T>A		intron_variant	Intron 14 of 19	5		ENSP00000376933.4

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

African (AFR) AF: 0.0242 AC: 1006 AN: 41546

American (AMR) AF: 0.114 AC: 1737 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0593 AC: 206 AN: 3472

East Asian (EAS) AF: 0.0757 AC: 391 AN: 5168

South Asian (SAS) AF: 0.105 AC: 507 AN: 4818

European-Finnish (FIN) AF: 0.0761 AC: 807 AN: 10602

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3628 AN: 68008

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

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
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16920467; hg19: chr11-94187926;