rs132771

Variant names:

• chr22-41629346-A-G
• rs132771
• NM_001469.5:c.195+1116A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001469.5(XRCC6):​c.195+1116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,206 control chromosomes in the GnomAD database, including 53,610 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 0.83 (53610 hom., cov: 33)
• Consequence: XRCC6 NM_001469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC6	NM_001469.5	c.195+1116A>G		intron_variant	Intron 3 of 12	ENST00000360079.8	NP_001460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC6	ENST00000360079.8	c.195+1116A>G		intron_variant	Intron 3 of 12	1	NM_001469.5	ENSP00000353192.3

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126434 AN: 152088 Hom.: 53548 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.831 AC: 126551 AN: 152206 Hom.: 53610 Cov.: 33 AF XY: 0.822 AC XY: 61155 AN XY: 74406

African (AFR) AF: 0.955 AC: 39669 AN: 41552

American (AMR) AF: 0.642 AC: 9786 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4893 AN: 5190

South Asian (SAS) AF: 0.700 AC: 3376 AN: 4826

European-Finnish (FIN) AF: 0.762 AC: 8060 AN: 10574

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55721 AN: 68026

Other (OTH) AF: 0.804 AC: 1699 AN: 2114

Alfa AF: 0.828 Hom.: 6541

Bravo AF: 0.825

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.067
DANN	Benign	0.36
PhyloP100		-4.0
Mutation Taster		=100/0	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: rs132771; hg19: chr22-42025350;