chr19-43543341-C-CGTGTGTGTGTGT

Variant names:

• chr19-43543341-C-CGTGTGTGTGTGT
• rs45592142
• ENST00000262887:c.*39_*50dupACACACACACAC

Variant summary

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

The NM_006297.3(XRCC1):​c.*39_*50dupACACACACACAC 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 0.0031 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (0 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 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.*39_*50dupACACACACACAC		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.*39_*50dupACACACACACAC		3_prime_UTR_variant	Exon 17 of 17	1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982	c.*39_*50dupACACACACACAC		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 437 AN: 139210 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00480

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00464

Gnomad FIN AF: 0.000224

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00289

Gnomad OTH AF: 0.00264

GnomAD4 exome AF: 0.00106 AC: 961 AN: 904890 Hom.: 0 Cov.: 0 AF XY: 0.00121 AC XY: 562 AN XY: 465622

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.000975

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.000126

Gnomad4 NFE exome AF: 0.000862

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00314 AC: 437 AN: 139312 Hom.: 2 Cov.: 0 AF XY: 0.00303 AC XY: 204 AN XY: 67314

Gnomad4 AFR AF: 0.00429

Gnomad4 AMR AF: 0.00479

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00465

Gnomad4 FIN AF: 0.000224

Gnomad4 NFE AF: 0.00289

Gnomad4 OTH AF: 0.00262

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;