rs17343819
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_020361.5(CPA6):āc.746A>Gā(p.Asn249Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,514,380 control chromosomes in the GnomAD database, including 14,764 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_020361.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPA6 | NM_020361.5 | c.746A>G | p.Asn249Ser | missense_variant, splice_region_variant | 7/11 | ENST00000297770.10 | |
ARFGEF1-DT | NR_136224.1 | n.694-6285T>C | intron_variant, non_coding_transcript_variant | ||||
CPA6 | XM_017013646.2 | c.302A>G | p.Asn101Ser | missense_variant, splice_region_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPA6 | ENST00000297770.10 | c.746A>G | p.Asn249Ser | missense_variant, splice_region_variant | 7/11 | 1 | NM_020361.5 | P1 | |
CPA6 | ENST00000518549.1 | n.960A>G | splice_region_variant, non_coding_transcript_exon_variant | 7/8 | 1 | ||||
CPA6 | ENST00000479862.6 | c.*342A>G | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 6/8 | 1 | ||||
CPA6 | ENST00000638254.1 | c.*342A>G | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.112 AC: 17099AN: 152124Hom.: 1135 Cov.: 32
GnomAD3 exomes AF: 0.112 AC: 27734AN: 247030Hom.: 1906 AF XY: 0.115 AC XY: 15336AN XY: 133476
GnomAD4 exome AF: 0.135 AC: 184404AN: 1362138Hom.: 13631 Cov.: 20 AF XY: 0.135 AC XY: 92233AN XY: 683486
GnomAD4 genome ? AF: 0.112 AC: 17092AN: 152242Hom.: 1133 Cov.: 32 AF XY: 0.108 AC XY: 8039AN XY: 74442
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 07, 2016 | - - |
Febrile seizures, familial, 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Familial temporal lobe epilepsy 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at