7-87402265-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_000443.4(ABCB4):c.3671G>A(p.Arg1224His) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,908 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 Uncertain significance (★★).
Frequency
Consequence
NM_000443.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251082Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135704
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461734Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727180
GnomAD4 genome AF: 0.000112 AC: 17AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74346
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.3671G>A (p.R1224H) alteration is located in exon 28 (coding exon 27) of the ABCB4 gene. This alteration results from a G to A substitution at nucleotide position 3671, causing the arginine (R) at amino acid position 1224 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1224 of the ABCB4 protein (p.Arg1224His). This variant is present in population databases (rs144790968, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ABCB4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1392644). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at