chr19-43543341-C-CGTGTGTGTGT

Variant names:

• chr19-43543341-C-CGTGTGTGTGT
• rs45592142
• ENST00000262887:c.*41_*50dupACACACACAC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006297.3(XRCC1):​c.*41_*50dupACACACACAC 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 (22 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (4 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.*41_*50dupACACACACAC		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.*41_*50dupACACACACAC		3_prime_UTR_variant	Exon 17 of 17	1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982	c.*41_*50dupACACACACAC		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.00877 AC: 1221 AN: 139196 Hom.: 22 Cov.: 0

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0258

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.00719

Gnomad FIN AF: 0.000784

Gnomad MID AF: 0.0232

Gnomad NFE AF: 0.00765

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00309 AC: 2791 AN: 904232 Hom.: 4 Cov.: 0 AF XY: 0.00328 AC XY: 1524 AN XY: 465224

Gnomad4 AFR exome AF: 0.00763

Gnomad4 AMR exome AF: 0.00396

Gnomad4 ASJ exome AF: 0.00728

Gnomad4 EAS exome AF: 0.000111

Gnomad4 SAS exome AF: 0.00452

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.00273

Gnomad4 OTH exome AF: 0.00465

GnomAD4 genome AF: 0.00877 AC: 1222 AN: 139298 Hom.: 22 Cov.: 0 AF XY: 0.00905 AC XY: 609 AN XY: 67300

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.000212

Gnomad4 SAS AF: 0.00720

Gnomad4 FIN AF: 0.000784

Gnomad4 NFE AF: 0.00767

Gnomad4 OTH AF: 0.00995

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;