22-41635949-C-G

Position:

• chr22-41635949-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001469.5(XRCC6):​c.196-164C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,060 control chromosomes in the GnomAD database, including 38,052 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 0.69 (38052 hom., cov: 32)
• Consequence: XRCC6 NM_001469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC6	NM_001469.5	c.196-164C>G		intron_variant		ENST00000360079.8	NP_001460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC6	ENST00000360079.8	c.196-164C>G		intron_variant		1	NM_001469.5	ENSP00000353192	P1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105213 AN: 151940 Hom.: 38046 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.691

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.692 AC: 105233 AN: 152060 Hom.: 38052 Cov.: 32 AF XY: 0.686 AC XY: 51012 AN XY: 74348

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.694

Alfa AF: 0.740 Hom.: 5349

Bravo AF: 0.666

Asia WGS AF: 0.767 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.34

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: rs132774; hg19: chr22-42031953;