rs1799780

chr19-43553124-G-A

Variant summary

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

The NM_006297.3(XRCC1):c.602-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,544,636 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.051 (264 hom., cov: 31)
  • Exomes 𝑓: 0.052 (2193 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.03

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.602-33C>T		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.602-33C>T		intron_variant		1	NM_006297.3	P1

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7785 AN: 152076 Hom.: 264 Cov.: 31

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0592

GnomAD3 exomes AF: 0.0722 AC: 11425 AN: 158310 Hom.: 493 AF XY: 0.0723 AC XY: 6011 AN XY: 83118

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0614

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.0892

Gnomad FIN exome AF: 0.0757

Gnomad NFE exome AF: 0.0491

Gnomad OTH exome AF: 0.0753

GnomAD4 exome AF: 0.0521 AC: 72492 AN: 1392442 Hom.: 2193 Cov.: 30 AF XY: 0.0531 AC XY: 36475 AN XY: 687518

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0614

Gnomad4 EAS exome AF: 0.0891

Gnomad4 SAS exome AF: 0.0885

Gnomad4 FIN exome AF: 0.0747

Gnomad4 NFE exome AF: 0.0452

Gnomad4 OTH exome AF: 0.0574

GnomAD4 genome AF: 0.0511 AC: 7782 AN: 152194 Hom.: 264 Cov.: 31 AF XY: 0.0550 AC XY: 4094 AN XY: 74394

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.0962

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0548 Hom.: 40

Bravo AF: 0.0526

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Laryngeal squamous cell carcinoma Other:1

association, no assertion criteria provided

clinical testing

Department Of Otolaryngology, First Affiliated Hospital Of Xinjiang Medical University

Jun 16, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.1
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1799780; hg19: chr19-44057276;