chr19-43543341-CGTGTGTGTGTGTGT-C

Variant names:

• chr19-43543341-CGTGTGTGTGTGTGT-C
• rs45592142
• NM_006297.3:c.*37_*50delACACACACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006297.3(XRCC1):​c.*37_*50delACACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,044,196 control chromosomes in the GnomAD database, including 1,028 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.054 (255 hom., cov: 0)
  • Exomes 𝑓: 0.063 (773 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 1.19
• Publications: 2 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.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0962 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.*37_*50delACACACACACACAC		3_prime_UTR	Exon 17 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.*37_*50delACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.*37_*50delACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.*37_*50delACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 7509 AN: 139188 Hom.: 255 Cov.: 0

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0202

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0595

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0629

GnomAD4 exome AF: 0.0627 AC: 56723 AN: 904906 Hom.: 773 AF XY: 0.0633 AC XY: 29474 AN XY: 465604

African (AFR) AF: 0.0304 AC: 635 AN: 20884

American (AMR) AF: 0.118 AC: 4427 AN: 37594

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 1338 AN: 20510

East Asian (EAS) AF: 0.0894 AC: 3210 AN: 35888

South Asian (SAS) AF: 0.0904 AC: 6362 AN: 70376

European-Finnish (FIN) AF: 0.0785 AC: 3122 AN: 39750

Middle Eastern (MID) AF: 0.156 AC: 610 AN: 3906

European-Non Finnish (NFE) AF: 0.0541 AC: 34360 AN: 634664

Other (OTH) AF: 0.0643 AC: 2659 AN: 41334

GnomAD4 genome AF: 0.0539 AC: 7507 AN: 139290 Hom.: 255 Cov.: 0 AF XY: 0.0584 AC XY: 3932 AN XY: 67296

African (AFR) AF: 0.0329 AC: 1174 AN: 35694

American (AMR) AF: 0.0888 AC: 1222 AN: 13764

Ashkenazi Jewish (ASJ) AF: 0.0595 AC: 201 AN: 3378

East Asian (EAS) AF: 0.104 AC: 489 AN: 4712

South Asian (SAS) AF: 0.104 AC: 448 AN: 4300

European-Finnish (FIN) AF: 0.0770 AC: 687 AN: 8922

Middle Eastern (MID) AF: 0.181 AC: 51 AN: 282

European-Non Finnish (NFE) AF: 0.0474 AC: 3100 AN: 65440

Other (OTH) AF: 0.0613 AC: 117 AN: 1908

Alfa AF: 0.0468 Hom.: 133

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Laryngeal squamous cell carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs45592142; hg19: chr19-44047493;