Variant rs11020802 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.45

Variant links:

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 links:

(HGNC:):

links:

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]

ANKRD49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	Effect	MANE	Protein	UniProt
MRE11	XM_011542837.3 linkuse as main transcript	c.-105-1053G>T	intron_variant		XP_011541139.1	P49959-1A0A024R395
	use as main transcript	n.94493959C>A	intergenic_region
ANKRD49	NM_017704.3 linkuse as main transcript	c.-167C>A	upstream_gene_variant	ENST00000544612.6	NP_060174.2	Q8WVL7A0A024R398
ANKRD49	XM_017017941.2 linkuse as main transcript	c.-302C>A	upstream_gene_variant		XP_016873430.1	Q8WVL7A0A024R398

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD49	ENST00000544612.6 linkuse as main transcript	c.-167C>A		upstream_gene_variant		1	NM_017704.3	ENSP00000440396.1		Q8WVL7

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47343

AN:

151946

Hom.:

7782

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.348

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.385

GnomAD4 genome

AF:

0.311

AC:

47348

AN:

152066

Hom.:

7782

Cov.:

AF XY:

0.317

AC XY:

23562

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.392

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.173

Hom.:

350

Bravo

AF:

0.307

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.094

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over