Genetic Variant ABCB1:p.Ser400Ile (chr7-87550493-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001348946.2(ABCB1):c.1199G>T(p.Ser400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S400N) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

176 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348946.2	MANE Select	c.1199G>T	p.Ser400Ile	missense	Exon 11 of 28	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.1409G>T	p.Ser470Ile	missense	Exon 15 of 32	NP_001335874.1
ABCB1	NM_000927.5		c.1199G>T	p.Ser400Ile	missense	Exon 12 of 29	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.1199G>T	p.Ser400Ile	missense	Exon 11 of 28	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.1199G>T	p.Ser400Ile	missense	Exon 12 of 29	ENSP00000265724.3	P08183-1
ABCB1	ENST00000890305.1		c.1199G>T	p.Ser400Ile	missense	Exon 10 of 27	ENSP00000560364.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.055

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

1.9

PhyloP100

0.070

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.50

Sift

Benign

0.090

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.42

MutPred

0.45

Loss of disorder (P = 0.021)

MVP

0.60

MPC

0.62

ClinPred

0.95

GERP RS

3.0

Varity_R

0.41

gMVP

0.67

Mutation Taster

=57/43

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over