rs72549401
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003742.4(ABCB11):c.1723C>T(p.Arg575Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,812 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_003742.4 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 |
---|---|---|---|---|---|---|---|
ABCB11 | NM_003742.4 | c.1723C>T | p.Arg575Ter | stop_gained | 15/28 | ENST00000650372.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB11 | ENST00000650372.1 | c.1723C>T | p.Arg575Ter | stop_gained | 15/28 | NM_003742.4 | P1 | ||
ABCB11 | ENST00000649448.1 | c.40C>T | p.Arg14Ter | stop_gained | 1/15 | ||||
ABCB11 | ENST00000478354.1 | n.461C>T | non_coding_transcript_exon_variant | 1/2 | 4 | ||||
ABCB11 | ENST00000439188.1 | c.*193C>T | 3_prime_UTR_variant, NMD_transcript_variant | 2/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 151934Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248568Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134846
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460878Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 726748
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74202
ClinVar
Submissions by phenotype
Benign recurrent intrahepatic cholestasis type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 28, 2024 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2023 | ClinVar contains an entry for this variant (Variation ID: 6589). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with progressive familial intrahepatic cholestasis (PMID: 9806540). This sequence change creates a premature translational stop signal (p.Arg575*) in the ABCB11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB11 are known to be pathogenic (PMID: 18395098, 20232290). This variant is present in population databases (rs72549401, gnomAD 0.03%). - |
Progressive familial intrahepatic cholestasis type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1998 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at