19-43551746-C-T

Variant names:

• chr19-43551746-C-T
• rs25486
• NM_006297.3:c.1083-59G>A

Variant summary

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

The NM_006297.3(XRCC1):​c.1083-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,315,072 control chromosomes in the GnomAD database, including 280,867 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 0.69 (36017 hom., cov: 31)
  • Exomes 𝑓: 0.65 (244850 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.1083-59G>A		intron	N/A	NP_006288.2	P18887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.1083-59G>A		intron	N/A	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.1077-59G>A		intron	N/A	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.1080-59G>A		intron	N/A	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104271 AN: 151756 Hom.: 35982 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.647 AC: 752408 AN: 1163198 Hom.: 244850 AF XY: 0.647 AC XY: 383033 AN XY: 592404

African (AFR) AF: 0.768 AC: 21138 AN: 27516

American (AMR) AF: 0.725 AC: 32114 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 14332 AN: 24174

East Asian (EAS) AF: 0.732 AC: 28061 AN: 38320

South Asian (SAS) AF: 0.645 AC: 51634 AN: 80046

European-Finnish (FIN) AF: 0.691 AC: 34916 AN: 50544

Middle Eastern (MID) AF: 0.707 AC: 3488 AN: 4932

European-Non Finnish (NFE) AF: 0.633 AC: 533325 AN: 842722

Other (OTH) AF: 0.659 AC: 33400 AN: 50664

GnomAD4 genome AF: 0.687 AC: 104352 AN: 151874 Hom.: 36017 Cov.: 31 AF XY: 0.691 AC XY: 51271 AN XY: 74200

African (AFR) AF: 0.771 AC: 31931 AN: 41406

American (AMR) AF: 0.680 AC: 10380 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3751 AN: 5150

South Asian (SAS) AF: 0.651 AC: 3136 AN: 4816

European-Finnish (FIN) AF: 0.698 AC: 7338 AN: 10514

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43615 AN: 67944

Other (OTH) AF: 0.688 AC: 1452 AN: 2110

Alfa AF: 0.702 Hom.: 15918

Bravo AF: 0.691

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs25486; hg19: chr19-44055898;