rs2229109

Variant names:

• chr7-87550493-C-A
• rs2229109
• NM_001348946.2:c.1199G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87550493-C-A
• chr7-87550493-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCB1 NM_001348946.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.1199G>T	p.Ser400Ile	missense_variant	Exon 11 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.1409G>T	p.Ser470Ile	missense_variant	Exon 15 of 32		NP_001335874.1
ABCB1	NM_000927.5	c.1199G>T	p.Ser400Ile	missense_variant	Exon 12 of 29		NP_000918.2
ABCB1	NM_001348944.2	c.1199G>T	p.Ser400Ile	missense_variant	Exon 13 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.1199G>T	p.Ser400Ile	missense_variant	Exon 11 of 28	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.1199G>T	p.Ser400Ile	missense_variant	Exon 12 of 29	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.1007G>T	p.Ser336Ile	missense_variant	Exon 11 of 28	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.055
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.0	.;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.090	.;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.42
MutPred		0.45		Loss of disorder (P = 0.021);Loss of disorder (P = 0.021);.;
MVP		0.60
MPC		0.62
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.41
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs2229109; hg19: chr7-87179809;