chr2-219172995-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_015680.6(CNPPD1):c.824G>A(p.Arg275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275C) has been classified as Uncertain significance.
Frequency
Consequence
NM_015680.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNPPD1 | NM_015680.6 | c.824G>A | p.Arg275His | missense_variant | Exon 8 of 8 | ENST00000360507.10 | NP_056495.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNPPD1 | ENST00000360507.10 | c.824G>A | p.Arg275His | missense_variant | Exon 8 of 8 | 1 | NM_015680.6 | ENSP00000353698.5 | ||
CNPPD1 | ENST00000409789.5 | c.824G>A | p.Arg275His | missense_variant | Exon 9 of 9 | 1 | ENSP00000386277.1 | |||
CNPPD1 | ENST00000453038.5 | c.824G>A | p.Arg275His | missense_variant | Exon 9 of 9 | 2 | ENSP00000410109.1 | |||
CNPPD1 | ENST00000451647.1 | c.*56G>A | downstream_gene_variant | 3 | ENSP00000405997.1 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250550Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135542
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461632Hom.: 0 Cov.: 71 AF XY: 0.0000138 AC XY: 10AN XY: 727104
GnomAD4 genome AF: 0.000210 AC: 32AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74400
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at