NM_000443.4:c.2925-433A>G

Variant names:

• chr7-87409825-T-C
• rs31658
• NM_000443.4:c.2925-433A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000443.4(ABCB4):​c.2925-433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,260 control chromosomes in the GnomAD database, including 56,955 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56955 hom., cov: 32)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.11
• Publications: 4 publications found

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]

ABCB4 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• gallbladder disease 1

  Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000443.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	NM_000443.4	MANE Select	c.2925-433A>G		intron	N/A	NP_000434.1	P21439-2
	ABCB4	NM_018849.3		c.2925-433A>G		intron	N/A	NP_061337.1	P21439-1
	ABCB4	NM_018850.3		c.2784-433A>G		intron	N/A	NP_061338.1	P21439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	ENST00000649586.2	MANE Select	c.2925-433A>G		intron	N/A	ENSP00000496956.2	P21439-2
	ABCB4	ENST00000265723.8	TSL:1	c.2925-433A>G		intron	N/A	ENSP00000265723.4	P21439-1
	ABCB4	ENST00000359206.8	TSL:1	c.2925-433A>G		intron	N/A	ENSP00000352135.3	P21439-2

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131394 AN: 152142 Hom.: 56923 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.883

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.864 AC: 131482 AN: 152260 Hom.: 56955 Cov.: 32 AF XY: 0.863 AC XY: 64234 AN XY: 74456

African (AFR) AF: 0.813 AC: 33768 AN: 41526

American (AMR) AF: 0.884 AC: 13519 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3134 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3719 AN: 5180

South Asian (SAS) AF: 0.886 AC: 4273 AN: 4822

European-Finnish (FIN) AF: 0.867 AC: 9199 AN: 10614

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60866 AN: 68028

Other (OTH) AF: 0.882 AC: 1864 AN: 2114

Alfa AF: 0.882 Hom.: 48541

Bravo AF: 0.860

Asia WGS AF: 0.803 AC: 2792 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0050
DANN	Benign	0.47
PhyloP100		-5.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs31658; hg19: chr7-87039141;