chr7-87443361-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000443.4(ABCB4):​c.1314G>A​(p.Thr438Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,614,046 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0050 ( 19 hom. )

Consequence

ABCB4
NM_000443.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -6.35
Variant links:
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 7-87443361-C-T is Benign according to our data. Variant chr7-87443361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 281138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.35 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00461 (702/152198) while in subpopulation AMR AF= 0.0068 (104/15284). AF 95% confidence interval is 0.00575. There are 6 homozygotes in gnomad4. There are 395 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCB4NM_000443.4 linkc.1314G>A p.Thr438Thr synonymous_variant Exon 12 of 28 ENST00000649586.2 NP_000434.1 P21439-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCB4ENST00000649586.2 linkc.1314G>A p.Thr438Thr synonymous_variant Exon 12 of 28 NM_000443.4 ENSP00000496956.2 P21439-2

Frequencies

GnomAD3 genomes
AF:
0.00462
AC:
702
AN:
152080
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00271
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00681
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0169
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00435
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00463
AC:
1164
AN:
251350
Hom.:
1
AF XY:
0.00462
AC XY:
627
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.00265
Gnomad AMR exome
AF:
0.00280
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0152
Gnomad NFE exome
AF:
0.00590
Gnomad OTH exome
AF:
0.00424
GnomAD4 exome
AF:
0.00497
AC:
7268
AN:
1461848
Hom.:
19
Cov.:
32
AF XY:
0.00481
AC XY:
3499
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00242
Gnomad4 AMR exome
AF:
0.00286
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0158
Gnomad4 NFE exome
AF:
0.00538
Gnomad4 OTH exome
AF:
0.00374
GnomAD4 genome
AF:
0.00461
AC:
702
AN:
152198
Hom.:
6
Cov.:
32
AF XY:
0.00531
AC XY:
395
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.00270
Gnomad4 AMR
AF:
0.00680
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0169
Gnomad4 NFE
AF:
0.00435
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00387
Hom.:
1
Bravo
AF:
0.00366
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00469
EpiControl
AF:
0.00492

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Feb 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ABCB4: BP4, BP7, BS2 -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:2
Feb 01, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Oct 19, 2015
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Cholestasis, intrahepatic, of pregnancy, 3 Benign:1
May 16, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Progressive familial intrahepatic cholestasis type 3 Benign:1
May 16, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.025
DANN
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45624933; hg19: chr7-87072677; API