19-43543341-CGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGT

Variant names:

• chr19-43543341-CGTGTGTGTGTGTGTGTGTGTGT-C
• rs45592142
• NM_006297.3:c.*29_*50delACACACACACACACACACACAC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006297.3(XRCC1):​c.*29_*50delACACACACACACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,044,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: XRCC1 NM_006297.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 24 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.*29_*50delACACACACACACACACACACAC		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.*29_*50delACACACACACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.*29_*50delACACACACACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.*29_*50delACACACACACACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.0000144 AC: 2 AN: 139220 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000265 AC: 24 AN: 905248 Hom.: 0 AF XY: 0.0000215 AC XY: 10 AN XY: 465798

African (AFR) AF: 0.00 AC: 0 AN: 20884

American (AMR) AF: 0.000372 AC: 14 AN: 37628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20522

East Asian (EAS) AF: 0.00 AC: 0 AN: 35914

South Asian (SAS) AF: 0.00 AC: 0 AN: 70440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.0000158 AC: 10 AN: 634840

Other (OTH) AF: 0.00 AC: 0 AN: 41346

GnomAD4 genome AF: 0.0000144 AC: 2 AN: 139220 Hom.: 0 Cov.: 0 AF XY: 0.0000298 AC XY: 2 AN XY: 67198

African (AFR) AF: 0.00 AC: 0 AN: 35584

American (AMR) AF: 0.00 AC: 0 AN: 13750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4726

South Asian (SAS) AF: 0.00 AC: 0 AN: 4310

European-Finnish (FIN) AF: 0.000112 AC: 1 AN: 8924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65460

Other (OTH) AF: 0.00 AC: 0 AN: 1894

Alfa AF: 0.00 Hom.: 133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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;