rs45593648
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000443.4(ABCB4):c.2395-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,602,136 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 1 hom. )
Consequence
ABCB4
NM_000443.4 intron
NM_000443.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.350
Genes affected
ABCB4 (HGNC:45): (ATP binding cassette subfamily B member 4) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 7-87418639-G-A is Benign according to our data. Variant chr7-87418639-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd4 at 5 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB4 | NM_000443.4 | c.2395-19C>T | intron_variant | ENST00000649586.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB4 | ENST00000649586.2 | c.2395-19C>T | intron_variant | NM_000443.4 | P1 | ||||
ABCB4 | ENST00000265723.8 | c.2395-19C>T | intron_variant | 1 | |||||
ABCB4 | ENST00000359206.8 | c.2395-19C>T | intron_variant | 1 | P1 | ||||
ABCB4 | ENST00000453593.5 | c.2395-19C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00250 AC: 380AN: 152164Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.000818 AC: 205AN: 250566Hom.: 0 AF XY: 0.000642 AC XY: 87AN XY: 135460
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GnomAD4 exome AF: 0.000308 AC: 446AN: 1449854Hom.: 1 Cov.: 29 AF XY: 0.000249 AC XY: 180AN XY: 722082
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GnomAD4 genome ? AF: 0.00250 AC: 380AN: 152282Hom.: 5 Cov.: 32 AF XY: 0.00220 AC XY: 164AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at