dbSNP rs13226726: ABCB1:c.287-7076G>A (chr7-87577299-C-T) – 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.287-7076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,110 control chromosomes in the GnomAD database, including 619 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 0.071 ( 619 hom., cov: 32)

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.290

Publications

6 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348946.2	MANE Select	c.287-7076G>A	intron	N/A	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.497-7076G>A	intron	N/A	NP_001335874.1
ABCB1	NM_000927.5		c.287-7076G>A	intron	N/A	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.287-7076G>A	intron	N/A	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.287-7076G>A	intron	N/A	ENSP00000265724.3	P08183-1
ABCB1	ENST00000890305.1		c.287-7076G>A	intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes

AF:

0.0712

AC:

10822

AN:

151992

Hom.:

619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0401

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0489

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

GnomAD4 genome

AF:

0.0711

AC:

10819

AN:

152110

Hom.:

619

Cov.:

AF XY:

0.0715

AC XY:

5319

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0163

AC:

675

AN:

41532

American (AMR)

AF:

0.0400

AC:

611

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.0243

AC:

117

AN:

4822

European-Finnish (FIN)

AF:

0.174

AC:

1834

AN:

10560

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7347

AN:

67972

Other (OTH)

AF:

0.0483

AC:

102

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

486

972

1457

1943

2429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0982

Hom.:

115

Bravo

AF:

0.0581

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.3

(source)

DANN

Benign

0.39

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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