Genetic Variant ABCB1:c.-330-3655A>G (chr7-87604733-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001348945.2(ABCB1):c.-154-1593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,136 control chromosomes in the GnomAD database, including 1,242 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 0.11 ( 1242 hom., cov: 32)

Consequence

ABCB1
NM_001348945.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.665

Publications

24 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=-0.75).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348945.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348945.2	c.-154-1593A>G	intron	N/A	NP_001335874.1
ABCB1	NM_000927.5	c.-330-3655A>G	intron	N/A	NP_000918.2
ABCB1	NM_001348944.2	c.-183-3655A>G	intron	N/A	NP_001335873.1	P08183-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000265724.8	TSL:1	c.-330-3655A>G	intron	N/A	ENSP00000265724.3	P08183-1
ABCB1	ENST00000961093.1		c.-184+913A>G	intron	N/A	ENSP00000631152.1
ABCB1	ENST00000543898.5	TSL:5	c.-330-3655A>G	intron	N/A	ENSP00000444095.1	P08183-2

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17100

AN:

152018

Hom.:

1237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0361

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.150

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

GnomAD4 genome

AF:

0.113

AC:

17123

AN:

152136

Hom.:

1242

Cov.:

AF XY:

0.115

AC XY:

8558

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0359

AC:

1491

AN:

41488

American (AMR)

AF:

0.221

AC:

3380

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3470

East Asian (EAS)

AF:

0.133

AC:

689

AN:

5180

South Asian (SAS)

AF:

0.137

AC:

659

AN:

4814

European-Finnish (FIN)

AF:

0.0781

AC:

828

AN:

10604

Middle Eastern (MID)

AF:

0.144

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.132

AC:

8974

AN:

67968

Other (OTH)

AF:

0.149

AC:

315

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

737

1474

2210

2947

3684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.126

Hom.:

2809

Bravo

AF:

0.117

Asia WGS

AF:

0.136

AC:

476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over