19-43543341-CGTGT-C

Position:

• chr19-43543341-CGTGT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006297.3(XRCC1):​c.*47_*50delACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,031,596 control chromosomes in the GnomAD database, including 5,014 homozygotes. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2333 hom., cov: 0)
  • Exomes 𝑓: 0.17 (2681 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.612

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.*47_*50delACAC		3_prime_UTR_variant	17/17	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887	c.*47_*50delACAC		3_prime_UTR_variant	17/17	1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982	c.*47_*50delACAC		3_prime_UTR_variant	16/16	2		ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 25510 AN: 138998 Hom.: 2335 Cov.: 0

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.173 AC: 154046 AN: 892494 Hom.: 2681 AF XY: 0.176 AC XY: 80571 AN XY: 458932

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.183 AC: 25525 AN: 139102 Hom.: 2333 Cov.: 0 AF XY: 0.184 AC XY: 12378 AN XY: 67208

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.180

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

- -

Computational scores

Source: dbNSFP v4.3

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: rs45592142; hg19: chr19-44047493;