chr19-43551413-G-A

Variant names:

• chr19-43551413-G-A
• rs3213369
• NM_006297.3:c.1199+158C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006297.3(XRCC1):​c.1199+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,258 control chromosomes in the GnomAD database, including 14 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 0.011 (14 hom., cov: 33)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 3 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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High AC in GnomAd4 at 1618 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.1199+158C>T		intron	N/A	NP_006288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.1199+158C>T		intron	N/A	ENSP00000262887.5
	XRCC1	ENST00000543982.5	TSL:2	c.1106+158C>T		intron	N/A	ENSP00000443671.1
	XRCC1	ENST00000597811.5	TSL:5	n.*471C>T		downstream_gene	N/A	ENSP00000470391.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1618 AN: 152140 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0149

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

GnomAD4 genome AF: 0.0106 AC: 1618 AN: 152258 Hom.: 14 Cov.: 33 AF XY: 0.0106 AC XY: 790 AN XY: 74454

African (AFR) AF: 0.00303 AC: 126 AN: 41558

American (AMR) AF: 0.00876 AC: 134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4826

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1060 AN: 68012

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.0157 Hom.: 9

Bravo AF: 0.0105

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.2
DANN	Benign	0.83
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism

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: rs3213369; hg19: chr19-44055565;