rs915927

Variant names:

• chr19-43553075-T-C
• rs915927
• NM_006297.3:c.618A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-43553075-T-C
• chr19-43553075-T-A
• chr19-43553075-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006297.3(XRCC1):​c.618A>G​(p.Pro206Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,576,866 control chromosomes in the GnomAD database, including 142,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12555 hom., cov: 32)
  • Exomes 𝑓: 0.42 (129985 hom.)
• Consequence: XRCC1 NM_006297.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.46
• Publications: 58 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-43553075-T-C is Benign according to our data. Variant chr19-43553075-T-C is described in ClinVar as Benign. ClinVar VariationId is 1684240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 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.618A>G	p.Pro206Pro	synonymous	Exon 7 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.618A>G	p.Pro206Pro	synonymous	Exon 7 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.618A>G	p.Pro206Pro	synonymous	Exon 7 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.615A>G	p.Pro205Pro	synonymous	Exon 7 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60741 AN: 151870 Hom.: 12547 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.366 AC: 70755 AN: 193098 AF XY: 0.375

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.420 AC: 598441 AN: 1424878 Hom.: 129985 Cov.: 50 AF XY: 0.421 AC XY: 296605 AN XY: 705218

African (AFR) AF: 0.397 AC: 13025 AN: 32846

American (AMR) AF: 0.220 AC: 8521 AN: 38702

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8649 AN: 25424

East Asian (EAS) AF: 0.103 AC: 3966 AN: 38434

South Asian (SAS) AF: 0.387 AC: 31614 AN: 81604

European-Finnish (FIN) AF: 0.455 AC: 23278 AN: 51124

Middle Eastern (MID) AF: 0.353 AC: 1646 AN: 4664

European-Non Finnish (NFE) AF: 0.443 AC: 484153 AN: 1093098

Other (OTH) AF: 0.400 AC: 23589 AN: 58982

GnomAD4 genome AF: 0.400 AC: 60793 AN: 151988 Hom.: 12555 Cov.: 32 AF XY: 0.397 AC XY: 29497 AN XY: 74286

African (AFR) AF: 0.395 AC: 16378 AN: 41438

American (AMR) AF: 0.301 AC: 4604 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3470

East Asian (EAS) AF: 0.115 AC: 593 AN: 5176

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4820

European-Finnish (FIN) AF: 0.460 AC: 4850 AN: 10550

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30112 AN: 67940

Other (OTH) AF: 0.389 AC: 821 AN: 2112

Alfa AF: 0.413 Hom.: 8616

Bravo AF: 0.382

Asia WGS AF: 0.258 AC: 904 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spinocerebellar ataxia, autosomal recessive 26 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.068
DANN	Benign	0.49
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs915927; hg19: chr19-44057227; COSMIC: COSV53447263; COSMIC: COSV53447263;