chr7-87411313-C-T

Position:

• chr7-87411313-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.2924+580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,064 control chromosomes in the GnomAD database, including 59,188 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 0.88 (59188 hom., cov: 30)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 (HGNC:):

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 = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB4	NM_000443.4	c.2924+580G>A		intron_variant		ENST00000649586.2	NP_000434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB4	ENST00000649586.2	c.2924+580G>A		intron_variant			NM_000443.4	ENSP00000496956.2
ABCB4	ENST00000265723.8	c.2924+580G>A		intron_variant		1		ENSP00000265723.4
ABCB4	ENST00000359206.8	c.2924+580G>A		intron_variant		1		ENSP00000352135.3
ABCB4	ENST00000453593.5	c.2784-1921G>A		intron_variant		5		ENSP00000392983.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133896 AN: 151946 Hom.: 59153 Cov.: 30

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.881 AC: 133986 AN: 152064 Hom.: 59188 Cov.: 30 AF XY: 0.880 AC XY: 65384 AN XY: 74328

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.889

Alfa AF: 0.894 Hom.: 76203

Bravo AF: 0.878

Asia WGS AF: 0.807 AC: 2809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.63

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: rs31659; hg19: chr7-87040629;