rs31672

Variant names:

• chr7-87430383-C-T
• rs31672
• NM_000443.4:c.1893+1021G>A

Variant summary

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

The NM_000443.4(ABCB4):​c.1893+1021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,050 control chromosomes in the GnomAD database, including 37,117 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 0.68 (37117 hom., cov: 32)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 8 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, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	NM_000443.4	MANE Select	c.1893+1021G>A		intron	N/A	NP_000434.1
	ABCB4	NM_018849.3		c.1893+1021G>A		intron	N/A	NP_061337.1
	ABCB4	NM_018850.3		c.1893+1021G>A		intron	N/A	NP_061338.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	ENST00000649586.2	MANE Select	c.1893+1021G>A		intron	N/A	ENSP00000496956.2
	ABCB4	ENST00000265723.8	TSL:1	c.1893+1021G>A		intron	N/A	ENSP00000265723.4
	ABCB4	ENST00000359206.8	TSL:1	c.1893+1021G>A		intron	N/A	ENSP00000352135.3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103253 AN: 151932 Hom.: 37121 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.679 AC: 103262 AN: 152050 Hom.: 37117 Cov.: 32 AF XY: 0.683 AC XY: 50752 AN XY: 74342

African (AFR) AF: 0.421 AC: 17416 AN: 41392

American (AMR) AF: 0.781 AC: 11931 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3556 AN: 5170

South Asian (SAS) AF: 0.745 AC: 3587 AN: 4818

European-Finnish (FIN) AF: 0.782 AC: 8290 AN: 10598

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53409 AN: 68006

Other (OTH) AF: 0.707 AC: 1489 AN: 2106

Alfa AF: 0.807 Hom.: 23916

Bravo AF: 0.666

Asia WGS AF: 0.703 AC: 2443 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		0.18
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: rs31672; hg19: chr7-87059699;