chr19-43543341-CGTGT-C

Variant names:

• chr19-43543341-CGTGT-C
• rs45592142
• NM_006297.3:c.*47_*50delACAC

Variant summary

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

The NM_006297.3(XRCC1):​c.*47_*50delACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,031,596 control chromosomes in the GnomAD database, including 5,014 homozygotes. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2333 hom., cov: 0)
  • Exomes 𝑓: 0.17 (2681 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.612
• 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 = 0.206 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.*47_*50delACAC		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.*47_*50delACAC		3_prime_UTR	Exon 17 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.*47_*50delACAC		3_prime_UTR	Exon 17 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.*47_*50delACAC		3_prime_UTR	Exon 17 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 25510 AN: 138998 Hom.: 2335 Cov.: 0

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.173 AC: 154046 AN: 892494 Hom.: 2681 AF XY: 0.176 AC XY: 80571 AN XY: 458932

African (AFR) AF: 0.146 AC: 3000 AN: 20608

American (AMR) AF: 0.107 AC: 3955 AN: 37100

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3104 AN: 20116

East Asian (EAS) AF: 0.148 AC: 5177 AN: 35040

South Asian (SAS) AF: 0.189 AC: 13052 AN: 69124

European-Finnish (FIN) AF: 0.218 AC: 8530 AN: 39134

Middle Eastern (MID) AF: 0.130 AC: 500 AN: 3844

European-Non Finnish (NFE) AF: 0.175 AC: 109749 AN: 626840

Other (OTH) AF: 0.172 AC: 6979 AN: 40688

GnomAD4 genome AF: 0.183 AC: 25525 AN: 139102 Hom.: 2333 Cov.: 0 AF XY: 0.184 AC XY: 12378 AN XY: 67208

African (AFR) AF: 0.158 AC: 5649 AN: 35644

American (AMR) AF: 0.120 AC: 1643 AN: 13746

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 519 AN: 3374

East Asian (EAS) AF: 0.117 AC: 552 AN: 4712

South Asian (SAS) AF: 0.218 AC: 936 AN: 4300

European-Finnish (FIN) AF: 0.253 AC: 2253 AN: 8898

Middle Eastern (MID) AF: 0.149 AC: 42 AN: 282

European-Non Finnish (NFE) AF: 0.206 AC: 13445 AN: 65346

Other (OTH) AF: 0.180 AC: 343 AN: 1910

Alfa AF: 0.148 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		0.61
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: rs45592142; hg19: chr19-44047493; COSMIC: COSV105017582;