rs7959887

Variant names:

• chr12-21184692-C-T
• rs7959887
• NM_006446.5:c.727+5672C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006446.5(SLCO1B1):​c.727+5672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 152,046 control chromosomes in the GnomAD database, including 923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.087 (923 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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.727+5672C>T		intron	N/A	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.727+5672C>T		intron	N/A	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.727+5672C>T		intron	N/A	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.727+5672C>T		intron	N/A	ENSP00000540243.1

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13277 AN: 151928 Hom.: 922 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0875 AC: 13300 AN: 152046 Hom.: 923 Cov.: 32 AF XY: 0.0899 AC XY: 6683 AN XY: 74338

African (AFR) AF: 0.155 AC: 6430 AN: 41470

American (AMR) AF: 0.117 AC: 1781 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1270 AN: 5156

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4812

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10592

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2190 AN: 67976

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0613 Hom.: 73

Bravo AF: 0.0969

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.61
DANN	Benign	0.26
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs7959887; hg19: chr12-21337626;