chr9-97697296-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000380.4(XPA):c.-4A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,597,438 control chromosomes in the GnomAD database, including 352,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000380.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
XPA | ENST00000375128.5 | c.-4A>G | 5_prime_UTR_variant | Exon 1 of 6 | 1 | NM_000380.4 | ENSP00000364270.5 | |||
XPA | ENST00000462523.5 | n.-4A>G | upstream_gene_variant | 5 | ENSP00000433006.1 | |||||
XPA | ENST00000496104.1 | n.-1A>G | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.692 AC: 105257AN: 152098Hom.: 37056 Cov.: 35
GnomAD3 exomes AF: 0.632 AC: 140577AN: 222442Hom.: 45079 AF XY: 0.627 AC XY: 77742AN XY: 123896
GnomAD4 exome AF: 0.659 AC: 951992AN: 1445222Hom.: 315647 Cov.: 80 AF XY: 0.654 AC XY: 470708AN XY: 719532
GnomAD4 genome AF: 0.692 AC: 105373AN: 152216Hom.: 37112 Cov.: 35 AF XY: 0.687 AC XY: 51166AN XY: 74434
ClinVar
Submissions by phenotype
not specified Benign:3
Variant summary: XPA c.-4A>G is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.64 in 251064 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 400 fold above the estimated maximal expected allele frequency for a pathogenic variant in XPA causing Xeroderma Pigmentosum phenotype (0.0016), strongly suggesting that the variant is benign. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
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not provided Benign:3
This variant is associated with the following publications: (PMID: 20865363, 19270000, 20056640, 15598786) -
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Xeroderma pigmentosum group A Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at