12-21176879-C-T

Variant names:

• chr12-21176879-C-T
• rs11045819
• NM_006446.5:c.463C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006446.5(SLCO1B1):​c.463C>T​(p.Pro155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P155T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLCO1B1 NM_006446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 149 publications found

Genes affected

SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

SLCO1B1 Gene-Disease associations (from GenCC):

• Rotor syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041882485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006446.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.463C>T	p.Pro155Ser	missense	Exon 5 of 15	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.463C>T	p.Pro155Ser	missense	Exon 5 of 15	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.463C>T	p.Pro155Ser	missense	Exon 6 of 16	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.463C>T	p.Pro155Ser	missense	Exon 6 of 16	ENSP00000540243.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250104 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1380200 Hom.: 0 Cov.: 27 AF XY: 0.00000145 AC XY: 1 AN XY: 689434

African (AFR) AF: 0.00 AC: 0 AN: 32450

American (AMR) AF: 0.00 AC: 0 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25064

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39406

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1037988

Other (OTH) AF: 0.00 AC: 0 AN: 57646

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.70
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		-0.81
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.021
Sift	Benign	0.47	T
Sift4G	Benign	0.88	T
Polyphen		0.0020	B
Vest4		0.083
MutPred		0.39		Gain of phosphorylation at P155 (P = 0.0563)
MVP		0.072
MPC		0.011
ClinPred		0.027	T
GERP RS		-3.4
Varity_R		0.061
gMVP		0.28
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11045819; hg19: chr12-21329813;