rs114402678
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2
The NM_020361.5(CPA6):c.809C>T(p.Ala270Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,614,054 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020361.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPA6 | NM_020361.5 | c.809C>T | p.Ala270Val | missense_variant | Exon 8 of 11 | ENST00000297770.10 | NP_065094.3 | |
CPA6 | XM_017013646.2 | c.365C>T | p.Ala122Val | missense_variant | Exon 8 of 11 | XP_016869135.1 | ||
ARFGEF1-DT | NR_136224.1 | n.694-7168G>A | intron_variant | Intron 4 of 4 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00282 AC: 429AN: 152102Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000736 AC: 185AN: 251474Hom.: 0 AF XY: 0.000552 AC XY: 75AN XY: 135910
GnomAD4 exome AF: 0.000315 AC: 460AN: 1461834Hom.: 0 Cov.: 30 AF XY: 0.000281 AC XY: 204AN XY: 727220
GnomAD4 genome AF: 0.00284 AC: 432AN: 152220Hom.: 2 Cov.: 32 AF XY: 0.00261 AC XY: 194AN XY: 74444
ClinVar
Submissions by phenotype
Febrile seizures, familial, 11 Pathogenic:1Uncertain:1Benign:1
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not provided Uncertain:1
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Intellectual disability Uncertain:1
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CPA6-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Familial temporal lobe epilepsy 5 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at