dbSNP rs3213619: ABCB1:c.-129T>C (chr7-87600877-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348946.2(ABCB1):c.-129T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 152,430 control chromosomes in the GnomAD database, including 211 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 0.051 ( 210 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1 hom. )

Consequence

ABCB1
NM_001348946.2 5_prime_UTR

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.417

Publications

151 publications found

Variant links:

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]

ABCB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ABCB1	NM_001348946.2 link	c.-129T>C	5_prime_UTR_variant	Exon 1 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5 link	c.-129T>C	5_prime_UTR_variant	Exon 2 of 29		NP_000918.2
ABCB1	NM_001348945.2 link	c.134-52T>C	intron_variant	Intron 4 of 31		NP_001335874.1
ABCB1	NM_001348944.2 link	c.-77-52T>C	intron_variant	Intron 2 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 link	c.-129T>C		5_prime_UTR_variant	Exon 1 of 28	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7747

AN:

152082

Hom.:

205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0846

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.0502

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0401

Gnomad OTH

AF:

0.0569

GnomAD4 exome

AF:

0.0261

AC:

AN:

230

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0319

AC:

AN:

188

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0511

AC:

7779

AN:

152200

Hom.:

210

Cov.:

AF XY:

0.0499

AC XY:

3711

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0851

AC:

3534

AN:

41538

American (AMR)

AF:

0.0334

AC:

511

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3466

East Asian (EAS)

AF:

0.0503

AC:

259

AN:

5152

South Asian (SAS)

AF:

0.0340

AC:

164

AN:

4818

European-Finnish (FIN)

AF:

0.0341

AC:

362

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2730

AN:

68008

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

385

770

1156

1541

1926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0438

Hom.:

470

Bravo

AF:

0.0514

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

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

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.35

PhyloP100

0.42

PromoterAI

0.13

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over