19-43556501-G-C

Variant names:

• chr19-43556501-G-C
• rs3213344
• NM_006297.3:c.256-1697C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006297.3(XRCC1):​c.256-1697C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,198 control chromosomes in the GnomAD database, including 631 homozygotes. 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: 𝑓 0.074 (631 hom., cov: 32)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.256-1697C>G		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.256-1697C>G		intron_variant	Intron 3 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.280-1697C>G		intron_variant	Intron 2 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11210 AN: 152080 Hom.: 631 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0737 AC: 11211 AN: 152198 Hom.: 631 Cov.: 32 AF XY: 0.0743 AC XY: 5530 AN XY: 74412

African (AFR) AF: 0.0642 AC: 2668 AN: 41552

American (AMR) AF: 0.102 AC: 1555 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1504 AN: 5162

South Asian (SAS) AF: 0.103 AC: 496 AN: 4818

European-Finnish (FIN) AF: 0.0369 AC: 391 AN: 10598

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4160 AN: 68000

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0313 Hom.: 17

Bravo AF: 0.0805

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3213344; hg19: chr19-44060653;