22-41635949-C-G

Variant names:

• chr22-41635949-C-G
• rs132774
• NM_001469.5:c.196-164C>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.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
• Publications: 25 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001469.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	NM_001469.5	MANE Select	c.196-164C>G		intron	N/A	NP_001460.1	P12956-1
	XRCC6	NM_001288976.2		c.196-164C>G		intron	N/A	NP_001275905.1	P12956-1
	XRCC6	NM_001288977.2		c.196-287C>G		intron	N/A	NP_001275906.1	P12956-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	ENST00000360079.8	TSL:1 MANE Select	c.196-164C>G		intron	N/A	ENSP00000353192.3	P12956-1
	XRCC6	ENST00000359308.8	TSL:1	c.196-164C>G		intron	N/A	ENSP00000352257.4	P12956-1
	XRCC6	ENST00000938034.1		c.196-164C>G		intron	N/A	ENSP00000608093.1

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

African (AFR) AF: 0.516 AC: 21398 AN: 41448

American (AMR) AF: 0.544 AC: 8298 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2444 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4753 AN: 5180

South Asian (SAS) AF: 0.653 AC: 3147 AN: 4818

European-Finnish (FIN) AF: 0.742 AC: 7845 AN: 10572

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55020 AN: 67992

Other (OTH) AF: 0.694 AC: 1465 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.34
PhyloP100		-0.93
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: rs132774; hg19: chr22-42031953;