ENST00000262887:c.*39_*50delACACACACACAC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000262887(XRCC1):​c.*39_*50delACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,044,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: XRCC1 ENST00000262887 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000503 AC: 70 AN: 139222 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.000528

GnomAD4 exome AF: 0.000275 AC: 249 AN: 905174 Hom.: 0 AF XY: 0.000283 AC XY: 132 AN XY: 465770

Gnomad4 AFR exome AF: 0.00187

Gnomad4 AMR exome AF: 0.000399

Gnomad4 ASJ exome AF: 0.0000487

Gnomad4 EAS exome AF: 0.000752

Gnomad4 SAS exome AF: 0.000568

Gnomad4 FIN exome AF: 0.000151

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.000339

GnomAD4 genome AF: 0.000502 AC: 70 AN: 139324 Hom.: 0 Cov.: 0 AF XY: 0.000490 AC XY: 33 AN XY: 67318

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00106

Gnomad4 SAS AF: 0.000232

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000138

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;