rs2307182

Variant names:

• chr19-43543687-C-T
• rs2307182
• NM_006297.3:c.1713G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_006297.3(XRCC1):​c.1713G>A​(p.Gly571Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,613,902 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: XRCC1 NM_006297.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0007974
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199
• Publications: 5 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-43543687-C-T is Benign according to our data. Variant chr19-43543687-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1675749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.199 with no splicing effect.
• BS2: High AC in GnomAd4 at 184 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.1713G>A	p.Gly571Gly	splice_region synonymous	Exon 16 of 17	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.1713G>A	p.Gly571Gly	splice_region synonymous	Exon 16 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.1725G>A	p.Gly575Gly	splice_region synonymous	Exon 16 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.1710G>A	p.Gly570Gly	splice_region synonymous	Exon 16 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 151972 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00125 AC: 313 AN: 251194 AF XY: 0.00125

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00164 AC: 2391 AN: 1461812 Hom.: 5 Cov.: 34 AF XY: 0.00163 AC XY: 1182 AN XY: 727216

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86256

European-Finnish (FIN) AF: 0.00206 AC: 110 AN: 53420

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.00191 AC: 2121 AN: 1111954

Other (OTH) AF: 0.00151 AC: 91 AN: 60394

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152090 Hom.: 0 Cov.: 31 AF XY: 0.000995 AC XY: 74 AN XY: 74354

African (AFR) AF: 0.000506 AC: 21 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00207 AC: 141 AN: 67994

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00164 Hom.: 4

Bravo AF: 0.00105

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00080
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.030		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: rs2307182; hg19: chr19-44047839;