22-41647092-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars. Variant chr22-41647092-G-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC6	NM_001469.5	c.960+10G>A		intron_variant		ENST00000360079.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC6	ENST00000360079.8	c.960+10G>A		intron_variant		1	NM_001469.5	P1

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 668 AN: 152132 Hom.: 3 Cov.: 31

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.: 7 AF XY: 0.00529 AC XY: 715 AN XY: 135278

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.: 35 Cov.: 30 AF XY: 0.00549 AC XY: 3986 AN XY: 726592

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.: 3 Cov.: 31 AF XY: 0.00442 AC XY: 329 AN XY: 74434

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.: 0

Bravo AF: 0.00424

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs150667139; hg19: chr22-42043096; COSMIC: COSV63158684; COSMIC: COSV63158684;