dbSNP rs10236274: ABCB1:c.2482-1528T>C (chr7-87533025-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001348946.2(ABCB1):c.2482-1528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,136 control chromosomes in the GnomAD database, including 1,397 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 0.10 ( 1397 hom., cov: 32)

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

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 Gene-Disease associations (from GenCC):

inflammatory bowel disease 13
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ABCB1 links:

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new If you want to explore the variant's impact on the transcript NM_001348946.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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.2482-1528T>C	intron	N/A	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.2692-1528T>C	intron	N/A	NP_001335874.1
ABCB1	NM_000927.5		c.2482-1528T>C	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.2482-1528T>C	intron	N/A	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.2482-1528T>C	intron	N/A	ENSP00000265724.3	P08183-1
ABCB1	ENST00000890305.1		c.2482-1528T>C	intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15648

AN:

152018

Hom.:

1390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0640

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0980

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

GnomAD4 genome

AF:

0.103

AC:

15668

AN:

152136

Hom.:

1397

Cov.:

AF XY:

0.106

AC XY:

7850

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.194

AC:

8029

AN:

41466

American (AMR)

AF:

0.105

AC:

1600

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3472

East Asian (EAS)

AF:

0.376

AC:

1946

AN:

5174

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4826

European-Finnish (FIN)

AF:

0.0640

AC:

678

AN:

10590

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2591

AN:

68020

Other (OTH)

AF:

0.101

AC:

213

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

653

1306

1958

2611

3264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0859

Hom.:

136

Bravo

AF:

0.114

Asia WGS

AF:

0.205

AC:

711

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.60

PhyloP100

0.042

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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