rs121909105
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_001374385.1(ATP8B1):c.1804C>T(p.Arg602Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001374385.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP8B1 | NM_001374385.1 | c.1804C>T | p.Arg602Ter | stop_gained | 16/28 | ENST00000648908.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP8B1 | ENST00000648908.2 | c.1804C>T | p.Arg602Ter | stop_gained | 16/28 | NM_001374385.1 | P1 | ||
ENST00000588925.5 | n.570+32797G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727192
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Progressive familial intrahepatic cholestasis type 1 Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 15, 2004 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Jun 15, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Rolfs Rare Disease Consulting, Rolfs Consulting Und Verwaltungs GmbH | Jan 01, 2019 | - - |
Benign recurrent intrahepatic cholestasis type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 30, 2023 | - - |
Familial intrahepatic cholestasis type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This sequence change creates a premature translational stop signal (p.Arg602*) in the ATP8B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP8B1 are known to be pathogenic (PMID: 15239083, 22525741). This variant is present in population databases (rs121909105, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of progressive familial intrahepatic cholestasis (PMID: 15239083, 33666275). ClinVar contains an entry for this variant (Variation ID: 7274). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at