7-87444459-G-T

Position:

• chr7-87444459-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000443.4(ABCB4):​c.1119+403C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,916 control chromosomes in the GnomAD database, including 37,124 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 0.67 (37124 hom., cov: 32)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB4	NM_000443.4	c.1119+403C>A		intron_variant		ENST00000649586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB4	ENST00000649586.2	c.1119+403C>A		intron_variant			NM_000443.4	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102515 AN: 151798 Hom.: 37133 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.675 AC: 102521 AN: 151916 Hom.: 37124 Cov.: 32 AF XY: 0.677 AC XY: 50248 AN XY: 74232

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.720

Alfa AF: 0.761 Hom.: 25598

Bravo AF: 0.659

Asia WGS AF: 0.677 AC: 2349 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.40

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: rs1149222; hg19: chr7-87073775; COSMIC: COSV55942402;