rs2097937

Variant names:

• chr7-87401587-G-A
• rs2097937
• XR_007060045.1:n.4237+246C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87401587-G-A
• chr7-87401587-G-C

Variant summary

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

The XR_007060045.1(ABCB4):​n.4237+246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 207,796 control chromosomes in the GnomAD database, including 57,797 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 0.71 (40063 hom., cov: 32)
  • Exomes 𝑓: 0.80 (17734 hom.)
• Consequence: ABCB4 XR_007060045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 16 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), Orphanet, ClinGen
• gallbladder disease 1

  Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649586.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	NM_000443.4	MANE Select	c.*509C>T		downstream_gene	N/A	NP_000434.1	P21439-2
	ABCB4	NM_018849.3		c.*509C>T		downstream_gene	N/A	NP_061337.1	P21439-1
	ABCB4	NM_018850.3		c.*509C>T		downstream_gene	N/A	NP_061338.1	P21439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	ENST00000649586.2	MANE Select	c.*509C>T		downstream_gene	N/A	ENSP00000496956.2	P21439-2
	ABCB4	ENST00000440025.1	TSL:3	c.*335C>T		downstream_gene	N/A	ENSP00000395716.1	H7C0M2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108024 AN: 151922 Hom.: 40067 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.795 AC: 44329 AN: 55754 Hom.: 17734 AF XY: 0.793 AC XY: 23367 AN XY: 29464

African (AFR) AF: 0.494 AC: 422 AN: 854

American (AMR) AF: 0.723 AC: 2560 AN: 3542

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 964 AN: 1138

East Asian (EAS) AF: 0.708 AC: 2104 AN: 2972

South Asian (SAS) AF: 0.752 AC: 6450 AN: 8582

European-Finnish (FIN) AF: 0.808 AC: 1956 AN: 2422

Middle Eastern (MID) AF: 0.794 AC: 127 AN: 160

European-Non Finnish (NFE) AF: 0.828 AC: 27598 AN: 33344

Other (OTH) AF: 0.784 AC: 2148 AN: 2740

GnomAD4 genome AF: 0.711 AC: 108048 AN: 152042 Hom.: 40063 Cov.: 32 AF XY: 0.712 AC XY: 52911 AN XY: 74330

African (AFR) AF: 0.476 AC: 19696 AN: 41414

American (AMR) AF: 0.783 AC: 11977 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2802 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3625 AN: 5174

South Asian (SAS) AF: 0.728 AC: 3509 AN: 4822

European-Finnish (FIN) AF: 0.792 AC: 8365 AN: 10560

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55457 AN: 67982

Other (OTH) AF: 0.751 AC: 1590 AN: 2116

Alfa AF: 0.775 Hom.: 97771

Bravo AF: 0.699

Asia WGS AF: 0.707 AC: 2453 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.41
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2097937; hg19: chr7-87030903;