rs2169969

Variant names:

• chr12-21182520-T-C
• rs2169969
• NM_006446.5:c.727+3500T>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.727+3500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,172 control chromosomes in the GnomAD database, including 1,521 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 0.12 (1521 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.727+3500T>C		intron_variant	Intron 7 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.727+3500T>C		intron_variant	Intron 7 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18578 AN: 152054 Hom.: 1524 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.122 AC: 18573 AN: 152172 Hom.: 1521 Cov.: 32 AF XY: 0.117 AC XY: 8734 AN XY: 74384

African (AFR) AF: 0.0398 AC: 1654 AN: 41560

American (AMR) AF: 0.109 AC: 1662 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3468

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5160

South Asian (SAS) AF: 0.0696 AC: 335 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12124 AN: 67976

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.128 Hom.: 248

Bravo AF: 0.120

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.83
PhyloP100		-0.83
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: rs2169969; hg19: chr12-21335454;