19-43543398-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_006297.3(XRCC1):c.1896A>G(p.Gln632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,587,640 control chromosomes in the GnomAD database, including 288,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (29553 hom., cov: 24)
  • Exomes 𝑓: 0.59 (258642 hom.)
• Consequence: XRCC1 NM_006297.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339

Genes affected

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 19-43543398-T-C is Benign according to our data. Variant chr19-43543398-T-C is described in ClinVar as [Benign]. Clinvar id is 1684239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.1896A>G	p.Gln632=	synonymous_variant	17/17	ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.1896A>G	p.Gln632=	synonymous_variant	17/17	1	NM_006297.3	P1
XRCC1	ENST00000543982.5	c.1803A>G	p.Gln601=	synonymous_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 93056 AN: 148772 Hom.: 29535 Cov.: 24

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.639

GnomAD3 exomes AF: 0.644 AC: 159895 AN: 248392 Hom.: 53159 AF XY: 0.634 AC XY: 85208 AN XY: 134342

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.891

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.545

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.593 AC: 853299 AN: 1438750 Hom.: 258642 Cov.: 37 AF XY: 0.592 AC XY: 424311 AN XY: 716604

Gnomad4 AFR exome AF: 0.664

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.896

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.625 AC: 93127 AN: 148890 Hom.: 29553 Cov.: 24 AF XY: 0.628 AC XY: 45527 AN XY: 72492

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.640

Alfa AF: 0.597 Hom.: 5866

Bravo AF: 0.649

Asia WGS AF: 0.748 AC: 2593 AN: 3474

EpiCase AF: 0.584

EpiControl AF: 0.578

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive 26 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	4.0
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3547; hg19: chr19-44047550; COSMIC: COSV53447140;