rs2229107

chr7-87509343-A-Cchr7-87509343-A-Gchr7-87509343-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001348946.2(ABCB1):c.3421T>G(p.Ser1141Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. 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. S1141T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB1 NM_001348946.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32436302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.3421T>G	p.Ser1141Ala	missense_variant	26/28	ENST00000622132.5
ABCB1	NM_001348945.2	c.3631T>G	p.Ser1211Ala	missense_variant	30/32
ABCB1	NM_000927.5	c.3421T>G	p.Ser1141Ala	missense_variant	27/29
ABCB1	NM_001348944.2	c.3421T>G	p.Ser1141Ala	missense_variant	28/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.3421T>G	p.Ser1141Ala	missense_variant	26/28	1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.61	T;.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Benign	1.5	L;L;.
MutationTaster	Benign	0.12	P;P
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.49		Loss of phosphorylation at S1141 (P = 0.0309);Loss of phosphorylation at S1141 (P = 0.0309);.;
MVP		0.54
MPC		0.18
ClinPred		0.14	T
GERP RS		3.6
Varity_R		0.13
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-87138659;