12-21215788-T-C

Variant names:

• chr12-21215788-T-C
• rs4363657
• NM_006446.5:c.1498-1331T>C

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1498-1331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,112 control chromosomes in the GnomAD database, including 2,889 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 0.18 (2889 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 104 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1498-1331T>C		intron_variant	Intron 11 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1498-1331T>C		intron_variant	Intron 11 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27705 AN: 151994 Hom.: 2887 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.182 AC: 27722 AN: 152112 Hom.: 2889 Cov.: 32 AF XY: 0.192 AC XY: 14259 AN XY: 74354

African (AFR) AF: 0.148 AC: 6123 AN: 41510

American (AMR) AF: 0.178 AC: 2719 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5166

South Asian (SAS) AF: 0.0884 AC: 427 AN: 4828

European-Finnish (FIN) AF: 0.321 AC: 3393 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11619 AN: 67982

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.175 Hom.: 10502

Bravo AF: 0.173

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.70
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: rs4363657; hg19: chr12-21368722;