19-43543341-CGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr19-43543341-C-CGTGTGT
• rs45592142
• ENST00000262887:c.*45_*50dupACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006297.3(XRCC1):​c.*45_*50dupACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0088 (18 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (2 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00879 (1225/139300) while in subpopulation AFR AF= 0.0195 (696/35684). AF 95% confidence interval is 0.0183. There are 18 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.*45_*50dupACACAC		3_prime_UTR_variant	Exon 17 of 17	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887	c.*45_*50dupACACAC		3_prime_UTR_variant	Exon 17 of 17	1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982	c.*45_*50dupACACAC		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.00879 AC: 1223 AN: 139198 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00997

Gnomad ASJ AF: 0.00385

Gnomad EAS AF: 0.00910

Gnomad SAS AF: 0.000928

Gnomad FIN AF: 0.00953

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00793

GnomAD4 exome AF: 0.00320 AC: 2890 AN: 904314 Hom.: 2 Cov.: 0 AF XY: 0.00310 AC XY: 1441 AN XY: 465314

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.00885

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.00852

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.00716

Gnomad4 NFE exome AF: 0.00197

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.00879 AC: 1225 AN: 139300 Hom.: 18 Cov.: 0 AF XY: 0.00866 AC XY: 583 AN XY: 67310

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.00385

Gnomad4 EAS AF: 0.00913

Gnomad4 SAS AF: 0.000929

Gnomad4 FIN AF: 0.00953

Gnomad4 NFE AF: 0.00354

Gnomad4 OTH AF: 0.00786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;