rs4148749

chr7-87515097-G-Cchr7-87515097-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):c.3282+134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,169,926 control chromosomes in the GnomAD database, including 1,356 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 0.053 (347 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1009 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.3282+134C>G		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.3282+134C>G		intron_variant
ABCB1	NM_001348944.2	c.3282+134C>G		intron_variant
ABCB1	NM_001348945.2	c.3492+134C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.3282+134C>G		intron_variant		1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8089 AN: 152160 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0316 AC: 32160 AN: 1017648 Hom.: 1009 AF XY: 0.0317 AC XY: 16299 AN XY: 514488

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0564

Gnomad4 ASJ exome AF: 0.0239

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.0457

Gnomad4 FIN exome AF: 0.0366

Gnomad4 NFE exome AF: 0.0209

Gnomad4 OTH exome AF: 0.0350

GnomAD4 genome AF: 0.0532 AC: 8099 AN: 152278 Hom.: 347 Cov.: 32 AF XY: 0.0537 AC XY: 3996 AN XY: 74478

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0435

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0166 Hom.: 17

Bravo AF: 0.0574

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.36

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: rs4148749; hg19: chr7-87144413;