NM_001348946.2:c.239C>G

Variant names:

• chr7-87585559-G-C
• rs9282565
• NM_001348946.2:c.239C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348946.2(ABCB1):​c.239C>G​(p.Ala80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB1 NM_001348946.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15617222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.239C>G	p.Ala80Gly	missense_variant	Exon 4 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.449C>G	p.Ala150Gly	missense_variant	Exon 8 of 32		NP_001335874.1
ABCB1	NM_000927.5	c.239C>G	p.Ala80Gly	missense_variant	Exon 5 of 29		NP_000918.2
ABCB1	NM_001348944.2	c.239C>G	p.Ala80Gly	missense_variant	Exon 6 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.239C>G	p.Ala80Gly	missense_variant	Exon 4 of 28	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.239C>G	p.Ala80Gly	missense_variant	Exon 5 of 29	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.239C>G	p.Ala80Gly	missense_variant	Exon 5 of 28	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.*95C>G		downstream_gene_variant		5		ENSP00000399419.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.84	T;.;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.65	N;N;N
PhyloP100		1.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.074	B;B;.
Vest4		0.10
MutPred		0.51		Loss of stability (P = 0.0564);Loss of stability (P = 0.0564);Loss of stability (P = 0.0564);
MVP		0.69
MPC		0.21
ClinPred		0.35	T
GERP RS		3.9
Varity_R		0.57
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs9282565; hg19: chr7-87214875;