19-43543341-CGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGT

Variant names:

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

Variant summary

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

The NM_006297.3(XRCC1):​c.*45_*50delACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,037,464 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (3 hom., cov: 0)
  • Exomes 𝑓: 0.024 (10 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0244 (21875/898202) while in subpopulation SAS AF= 0.0281 (1958/69784). AF 95% confidence interval is 0.027. There are 10 homozygotes in gnomad4_exome. There are 11434 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 161 AN: 139160 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000509

Gnomad ASJ AF: 0.000592

Gnomad EAS AF: 0.000635

Gnomad SAS AF: 0.000929

Gnomad FIN AF: 0.00124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000642

Gnomad OTH AF: 0.000529

GnomAD4 exome AF: 0.0244 AC: 21875 AN: 898202 Hom.: 10 AF XY: 0.0247 AC XY: 11434 AN XY: 462066

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.0281

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.00116 AC: 161 AN: 139262 Hom.: 3 Cov.: 0 AF XY: 0.00122 AC XY: 82 AN XY: 67286

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.000508

Gnomad4 ASJ AF: 0.000592

Gnomad4 EAS AF: 0.000637

Gnomad4 SAS AF: 0.000930

Gnomad4 FIN AF: 0.00124

Gnomad4 NFE AF: 0.000642

Gnomad4 OTH AF: 0.000524

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;