rs31672

Positions:

• chr7-87430383-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB4	NM_000443.4	c.1893+1021G>A		intron_variant		ENST00000649586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB4	ENST00000649586.2	c.1893+1021G>A		intron_variant			NM_000443.4	P1

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

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.707

Alfa AF: 0.806 Hom.: 21708

Bravo AF: 0.666

Asia WGS AF: 0.703 AC: 2443 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs31672; hg19: chr7-87059699;