rs4148733

Variant names:

• chr7-87583916-A-G
• rs4148733
• NM_001348946.2:c.286+1596T>C

Variant summary

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

The NM_001348946.2(ABCB1):​c.286+1596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,166 control chromosomes in the GnomAD database, including 2,311 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 0.17 (2311 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 12 publications found

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) 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. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

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 (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.286+1596T>C		intron_variant	Intron 4 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.496+1596T>C		intron_variant	Intron 8 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.286+1596T>C		intron_variant	Intron 5 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.286+1596T>C		intron_variant	Intron 6 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.286+1596T>C		intron_variant	Intron 4 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.286+1596T>C		intron_variant	Intron 5 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.286+1596T>C		intron_variant	Intron 5 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25467 AN: 152048 Hom.: 2300 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.168 AC: 25511 AN: 152166 Hom.: 2311 Cov.: 32 AF XY: 0.170 AC XY: 12639 AN XY: 74390

African (AFR) AF: 0.191 AC: 7922 AN: 41498

American (AMR) AF: 0.254 AC: 3882 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3470

East Asian (EAS) AF: 0.120 AC: 621 AN: 5186

South Asian (SAS) AF: 0.141 AC: 680 AN: 4832

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9865 AN: 67994

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.160 Hom.: 3544

Bravo AF: 0.176

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.57
PhyloP100		-0.20
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: rs4148733; hg19: chr7-87213232;