Variant 22-41647092-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001469.5(XRCC6):c.960+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,612,638 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0053 ( 35 hom. )

Consequence

XRCC6
NM_001469.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.305

Variant links:

Genes affected

XRCC6 (HGNC:4055): (X-ray repair cross complementing 6) The p70/p80 autoantigen is a nuclear complex consisting of two subunits with molecular masses of approximately 70 and 80 kDa. The complex functions as a single-stranded DNA-dependent ATP-dependent helicase. The complex may be involved in the repair of nonhomologous DNA ends such as that required for double-strand break repair, transposition, and V(D)J recombination. High levels of autoantibodies to p70 and p80 have been found in some patients with systemic lupus erythematosus. [provided by RefSeq, Jul 2008]

XRCC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-41647092-G-A is Benign according to our data. Variant chr22-41647092-G-A is described in ClinVar as [Benign]. Clinvar id is 779050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41647092-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC6	NM_001469.5 linkuse as main transcript	c.960+10G>A		intron_variant		ENST00000360079.8	NP_001460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC6	ENST00000360079.8 linkuse as main transcript	c.960+10G>A		intron_variant		1	NM_001469.5	ENSP00000353192	P1	P12956-1

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

668

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00600

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00475

AC:

1187

AN:

249708

Hom.:

AF XY:

0.00529

AC XY:

715

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.000877

Gnomad AMR exome

AF:

0.00458

Gnomad ASJ exome

AF:

0.00822

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00853

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00546

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00532

AC:

7771

AN:

1460388

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

3986

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00967

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00819

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00548

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.00439

AC:

668

AN:

152250

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00753

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00789

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00600

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00540

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.00289

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

DANN

Benign

0.87

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