rs45593648

Variant names:

• chr7-87418639-G-A
• rs45593648
• NM_000443.4:c.2395-19C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000443.4(ABCB4):​c.2395-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,602,136 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.350

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-87418639-G-A is Benign according to our data. Variant chr7-87418639-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0025 (380/152282) while in subpopulation AFR AF= 0.00852 (354/41560). AF 95% confidence interval is 0.00779. There are 5 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB4	NM_000443.4	c.2395-19C>T		intron_variant	Intron 19 of 27	ENST00000649586.2	NP_000434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB4	ENST00000649586.2	c.2395-19C>T		intron_variant	Intron 19 of 27		NM_000443.4	ENSP00000496956.2
ABCB4	ENST00000265723.8	c.2395-19C>T		intron_variant	Intron 19 of 27	1		ENSP00000265723.4
ABCB4	ENST00000359206.8	c.2395-19C>T		intron_variant	Intron 19 of 27	1		ENSP00000352135.3
ABCB4	ENST00000453593.5	c.2395-19C>T		intron_variant	Intron 18 of 25	5		ENSP00000392983.1

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 152164 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00854

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000818 AC: 205 AN: 250566 Hom.: 0 AF XY: 0.000642 AC XY: 87 AN XY: 135460

Gnomad AFR exome AF: 0.00975

Gnomad AMR exome AF: 0.000812

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000383

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000308 AC: 446 AN: 1449854 Hom.: 1 Cov.: 29 AF XY: 0.000249 AC XY: 180 AN XY: 722082

Gnomad4 AFR exome AF: 0.00875

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000245

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152282 Hom.: 5 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74460

Gnomad4 AFR AF: 0.00852

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00292

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 05, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.65

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: rs45593648; hg19: chr7-87047955;