rs72552780
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000443.4(ABCB4):c.430C>T(p.Arg144Ter) 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 1,613,632 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_000443.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB4 | NM_000443.4 | c.430C>T | p.Arg144Ter | stop_gained | 6/28 | ENST00000649586.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB4 | ENST00000649586.2 | c.430C>T | p.Arg144Ter | stop_gained | 6/28 | NM_000443.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151794Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251350Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461838Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727216
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151794Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74092
ClinVar
Submissions by phenotype
Cholestasis, intrahepatic, of pregnancy, 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2009 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 13696). This premature translational stop signal has been observed in individual(s) with ABCB4-related conditions (PMID: 12624161, 26153658). This variant is present in population databases (rs72552780, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg144*) in the ABCB4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB4 are known to be pathogenic (PMID: 17726488, 25755532). - |
Progressive familial intrahepatic cholestasis type 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Rolfs Rare Disease Consulting, Rolfs Consulting Und Verwaltungs GmbH | Jan 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at