rs11020802

Variant names:

• chr11-94493959-C-A
• rs11020802
• XM_011542837.3:c.-105-1053G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-94493959-C-A
• chr11-94493959-C-G
• chr11-94493959-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_011542837.3(MRE11):​c.-105-1053G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,126 control chromosomes in the GnomAD database, including 7,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7782 hom., cov: 33)
  • Exomes 𝑓: 0.35 (5 hom.)
• Consequence: MRE11 XM_011542837.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• Publications: 16 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]

ANKRD49 (HGNC:25970): (ankyrin repeat domain 49) Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-94493959-C-A is Benign according to our data. Variant chr11-94493959-C-A is described in ClinVar as Benign. ClinVar VariationId is 1291079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.-274G>T		upstream_gene_variant		ENST00000323929.8	NP_005582.1
ANKRD49	NM_017704.3	c.-167C>A		upstream_gene_variant		ENST00000544612.6	NP_060174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.-274G>T		upstream_gene_variant		1	NM_005591.4	ENSP00000325863.4
ANKRD49	ENST00000544612.6	c.-167C>A		upstream_gene_variant		1	NM_017704.3	ENSP00000440396.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47343 AN: 151946 Hom.: 7782 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.350 AC: 21 AN: 60 Hom.: 5 Cov.: 0 AF XY: 0.348 AC XY: 16 AN XY: 46

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.385 AC: 20 AN: 52

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.311 AC: 47348 AN: 152066 Hom.: 7782 Cov.: 33 AF XY: 0.317 AC XY: 23562 AN XY: 74328

African (AFR) AF: 0.206 AC: 8548 AN: 41508

American (AMR) AF: 0.395 AC: 6030 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2017 AN: 5148

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4822

European-Finnish (FIN) AF: 0.399 AC: 4214 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22531 AN: 67962

Other (OTH) AF: 0.333 AC: 701 AN: 2108

Alfa AF: 0.176 Hom.: 373

Bravo AF: 0.307

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.094
DANN	Benign	0.53
PhyloP100		-1.4
PromoterAI		-0.053	Neutral
Mutation Taster		=300/0	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: rs11020802; hg19: chr11-94227125; COSMIC: COSV57060822;