chr19-43554989-G-A

Variant names:

• chr19-43554989-G-A
• rs1799778
• NM_006297.3:c.256-185C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006297.3(XRCC1):​c.256-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 20 publications found

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]

XRCC1 Gene-Disease associations (from GenCC):

• head and neck cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spinocerebellar ataxia, autosomal recessive 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000268361 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.256-185C>T		intron_variant	Intron 3 of 16	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.256-185C>T		intron_variant	Intron 3 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.280-185C>T		intron_variant	Intron 2 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 361404 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 188124

African (AFR) AF: 0.00 AC: 0 AN: 9964

American (AMR) AF: 0.00 AC: 0 AN: 12174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11046

East Asian (EAS) AF: 0.00 AC: 0 AN: 25460

South Asian (SAS) AF: 0.00 AC: 0 AN: 25466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 230662

Other (OTH) AF: 0.00 AC: 0 AN: 20842

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 4320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.3
DANN	Benign	0.79
PhyloP100		-0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1799778; hg19: chr19-44059141;