Genetic Variant XRCC1:c.*49_*50dupAC (chr19-43543341-C-CGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006297.3(XRCC1):c.*49_*50dupAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 826 hom., cov: 0)

Exomes 𝑓: 0.047 ( 38 hom. )

Consequence

XRCC1
NM_006297.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.49_50dupAC		3_prime_UTR_variant	Exon 17 of 17	ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887 link	c.49_50dupAC		3_prime_UTR_variant	Exon 17 of 17	1	NM_006297.3	ENSP00000262887.5		P18887
XRCC1	ENST00000543982 link	c.49_50dupAC		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000443671.1		F5H8D7

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

12710

AN:

139066

Hom.:

830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.0619

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0269

Gnomad SAS

AF:

0.0825

Gnomad FIN

AF:

0.0304

Gnomad MID

AF:

0.0927

Gnomad NFE

AF:

0.0625

Gnomad OTH

AF:

0.0776

GnomAD4 exome

AF:

0.0468

AC:

42064

AN:

898472

Hom.:

Cov.:

AF XY:

0.0484

AC XY:

22382

AN XY:

462310

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0634

Gnomad4 ASJ exome

AF:

0.0550

Gnomad4 EAS exome

AF:

0.0362

Gnomad4 SAS exome

AF:

0.0645

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0542

GnomAD4 genome

AF:

0.0914

AC:

12722

AN:

139164

Hom.:

826

Cov.:

AF XY:

0.0889

AC XY:

5980

AN XY:

67238

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0619

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.0270

Gnomad4 SAS

AF:

0.0814

Gnomad4 FIN

AF:

0.0304

Gnomad4 NFE

AF:

0.0625

Gnomad4 OTH

AF:

0.0775

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

19-43543341-CGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over