chr19-43543341-CGTGTGTGTGTGT-C

Variant names:

• chr19-43543341-CGTGTGTGTGTGT-C
• rs45592142
• NM_006297.3:c.*39_*50delACACACACACAC

Variant summary

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

The NM_006297.3(XRCC1):​c.*39_*50delACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,044,498 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 0.00050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (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 GnomAd4 at 70 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.*39_*50delACACACACACAC		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.*39_*50delACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.*39_*50delACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.*39_*50delACACACACACAC		3_prime_UTR	Exon 17 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.000503 AC: 70 AN: 139222 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.000528

GnomAD4 exome AF: 0.000275 AC: 249 AN: 905174 Hom.: 0 AF XY: 0.000283 AC XY: 132 AN XY: 465770

African (AFR) AF: 0.00187 AC: 39 AN: 20884

American (AMR) AF: 0.000399 AC: 15 AN: 37622

Ashkenazi Jewish (ASJ) AF: 0.0000487 AC: 1 AN: 20522

East Asian (EAS) AF: 0.000752 AC: 27 AN: 35908

South Asian (SAS) AF: 0.000568 AC: 40 AN: 70428

European-Finnish (FIN) AF: 0.000151 AC: 6 AN: 39762

Middle Eastern (MID) AF: 0.000512 AC: 2 AN: 3906

European-Non Finnish (NFE) AF: 0.000165 AC: 105 AN: 634798

Other (OTH) AF: 0.000339 AC: 14 AN: 41344

GnomAD4 genome AF: 0.000502 AC: 70 AN: 139324 Hom.: 0 Cov.: 0 AF XY: 0.000490 AC XY: 33 AN XY: 67318

African (AFR) AF: 0.00151 AC: 54 AN: 35698

American (AMR) AF: 0.00 AC: 0 AN: 13772

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

East Asian (EAS) AF: 0.00106 AC: 5 AN: 4712

South Asian (SAS) AF: 0.000232 AC: 1 AN: 4304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000138 AC: 9 AN: 65452

Other (OTH) AF: 0.000524 AC: 1 AN: 1910

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
Mutation Taster		=100/0	polymorphism

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;