7-87569949-T-A

Variant names:

• chr7-87569949-T-A
• rs2235020
• NM_001348946.2:c.338+223A>T

Variant summary

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

The ENST00000622132.5(ABCB1):​c.338+223A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,850 control chromosomes in the GnomAD database, including 12,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: 𝑓 0.38 (12077 hom., cov: 32)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.161
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.338+223A>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.548+223A>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.338+223A>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.338+223A>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.338+223A>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.338+223A>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57875 AN: 151732 Hom.: 12088 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.381 AC: 57869 AN: 151850 Hom.: 12077 Cov.: 32 AF XY: 0.387 AC XY: 28723 AN XY: 74212

African (AFR) AF: 0.205 AC: 8492 AN: 41468

American (AMR) AF: 0.419 AC: 6385 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3468

East Asian (EAS) AF: 0.636 AC: 3271 AN: 5146

South Asian (SAS) AF: 0.593 AC: 2859 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5070 AN: 10502

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29282 AN: 67880

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.257 Hom.: 645

Bravo AF: 0.370

Asia WGS AF: 0.573 AC: 1984 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.16
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: rs2235020; hg19: chr7-87199265;