7-87402374-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000443.4(ABCB4):c.3634-72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,550,348 control chromosomes in the GnomAD database, including 8,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1890 hom., cov: 33)
  • Exomes 𝑓: 0.085 (6130 hom.)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.915

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-87402374-A-G is Benign according to our data. Variant chr7-87402374-A-G is described in ClinVar as [Benign]. Clinvar id is 1183441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB4	NM_000443.4	c.3634-72T>C		intron_variant		ENST00000649586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB4	ENST00000649586.2	c.3634-72T>C		intron_variant			NM_000443.4	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20136 AN: 152124 Hom.: 1885 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0845 AC: 118163 AN: 1398106 Hom.: 6130 AF XY: 0.0858 AC XY: 59589 AN XY: 694310

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.0893

Gnomad4 ASJ exome AF: 0.0846

Gnomad4 EAS exome AF: 0.0123

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0739

Gnomad4 NFE exome AF: 0.0759

Gnomad4 OTH exome AF: 0.0921

GnomAD4 genome AF: 0.132 AC: 20171 AN: 152242 Hom.: 1890 Cov.: 33 AF XY: 0.131 AC XY: 9754 AN XY: 74446

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0753

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.116

Alfa AF: 0.115 Hom.: 171

Bravo AF: 0.138

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.8
Dann	Benign	0.86

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: rs45549641; hg19: chr7-87031690;