7-87411313-C-T

Variant names:

• chr7-87411313-C-T
• rs31659
• NM_000443.4:c.2924+580G>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.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
• Publications: 3 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=-0.9).
• 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 rank	MANE	Protein	UniProt
ABCB4	NM_000443.4	c.2924+580G>A		intron_variant	Intron 23 of 27	ENST00000649586.2	NP_000434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB4	ENST00000649586.2	c.2924+580G>A		intron_variant	Intron 23 of 27		NM_000443.4	ENSP00000496956.2
ABCB4	ENST00000265723.8	c.2924+580G>A		intron_variant	Intron 23 of 27	1		ENSP00000265723.4
ABCB4	ENST00000359206.8	c.2924+580G>A		intron_variant	Intron 23 of 27	1		ENSP00000352135.3
ABCB4	ENST00000453593.5	c.2784-1921G>A		intron_variant	Intron 21 of 25	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

African (AFR) AF: 0.877 AC: 36348 AN: 41458

American (AMR) AF: 0.886 AC: 13531 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3130 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3677 AN: 5152

South Asian (SAS) AF: 0.886 AC: 4276 AN: 4824

European-Finnish (FIN) AF: 0.867 AC: 9162 AN: 10566

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

European-Non Finnish (NFE) AF: 0.895 AC: 60846 AN: 68008

Other (OTH) AF: 0.889 AC: 1876 AN: 2110

Alfa AF: 0.893 Hom.: 97327

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
PhyloP100		-0.32
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: rs31659; hg19: chr7-87040629;