rs1202168

Variant names:

• chr7-87566646-G-A
• rs1202168
• NM_001348946.2:c.530+139C>T

Variant summary

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

The NM_001348946.2(ABCB1):​c.530+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 850,844 control chromosomes in the GnomAD database, including 87,500 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 0.40 (12761 hom., cov: 31)
  • Exomes 𝑓: 0.45 (74739 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.141
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.530+139C>T		intron_variant	Intron 6 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.740+139C>T		intron_variant	Intron 10 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.530+139C>T		intron_variant	Intron 7 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.530+139C>T		intron_variant	Intron 8 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.530+139C>T		intron_variant	Intron 6 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.530+139C>T		intron_variant	Intron 7 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.339-405C>T		intron_variant	Intron 6 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60239 AN: 151858 Hom.: 12773 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.455 AC: 317944 AN: 698868 Hom.: 74739 AF XY: 0.463 AC XY: 170035 AN XY: 367562

African (AFR) AF: 0.244 AC: 4459 AN: 18312

American (AMR) AF: 0.481 AC: 16254 AN: 33798

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 7130 AN: 19782

East Asian (EAS) AF: 0.621 AC: 20269 AN: 32652

South Asian (SAS) AF: 0.610 AC: 38128 AN: 62546

European-Finnish (FIN) AF: 0.480 AC: 17944 AN: 37412

Middle Eastern (MID) AF: 0.448 AC: 1732 AN: 3862

European-Non Finnish (NFE) AF: 0.431 AC: 196461 AN: 455398

Other (OTH) AF: 0.443 AC: 15567 AN: 35106

GnomAD4 genome AF: 0.396 AC: 60234 AN: 151976 Hom.: 12761 Cov.: 31 AF XY: 0.403 AC XY: 29907 AN XY: 74284

African (AFR) AF: 0.250 AC: 10363 AN: 41442

American (AMR) AF: 0.431 AC: 6575 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3287 AN: 5164

South Asian (SAS) AF: 0.604 AC: 2898 AN: 4798

European-Finnish (FIN) AF: 0.484 AC: 5114 AN: 10562

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29471 AN: 67962

Other (OTH) AF: 0.388 AC: 818 AN: 2108

Alfa AF: 0.423 Hom.: 23612

Bravo AF: 0.386

Asia WGS AF: 0.578 AC: 2005 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.32
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1202168; hg19: chr7-87195962;