Genetic Variant XRCC1:c.*50_*51insACACACACACACACACACACACACACACACACACACACACACACACACACAC (chr19-43543341-C-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006297.3(XRCC1):c.*50_*51insACACACACACACACACACACACACACACACACACACACACACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: not found (cov: 0)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

XRCC1
NM_006297.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Publications

0 publications found

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 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)

XRCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.50_51insACACACACACACACACACACACACACACACACACACACACACACACACACAC		3_prime_UTR	Exon 17 of 17	NP_006288.2	P18887

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.50_51insACACACACACACACACACACACACACACACACACACACACACACACACACAC	3_prime_UTR	Exon 17 of 17	ENSP00000262887.5	P18887
XRCC1	ENST00000953258.1		c.50_51insACACACACACACACACACACACACACACACACACACACACACACACACACAC	3_prime_UTR	Exon 17 of 17	ENSP00000623317.1
XRCC1	ENST00000865401.1		c.50_51insACACACACACACACACACACACACACACACACACACACACACACACACACAC	3_prime_UTR	Exon 17 of 17	ENSP00000535460.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000110

AC:

AN:

905250

Hom.:

Cov.:

AF XY:

0.00000215

AC XY:

AN XY:

465798

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000479

AC:

AN:

20884

American (AMR)

AF:

0.00

AC:

AN:

37628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20522

East Asian (EAS)

AF:

0.00

AC:

AN:

35914

South Asian (SAS)

AF:

0.00

AC:

AN:

70440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3906

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

634842

Other (OTH)

AF:

0.00

AC:

AN:

41346

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

Splicing

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

Publications

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19-43543341-CGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over