12-21147068-T-G

Variant names:

• chr12-21147068-T-G
• rs11045787
• NM_006446.5:c.84+5410T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006446.5(SLCO1B1):​c.84+5410T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,206 control chromosomes in the GnomAD database, including 1,786 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 0.13 (1786 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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]

ENSG00000257062 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.84+5410T>G		intron_variant	Intron 2 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.84+5410T>G		intron_variant	Intron 2 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*141+5410T>G		intron_variant	Intron 5 of 5	4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19809 AN: 152088 Hom.: 1788 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.130 AC: 19797 AN: 152206 Hom.: 1786 Cov.: 32 AF XY: 0.124 AC XY: 9236 AN XY: 74432

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.150

Alfa AF: 0.158 Hom.: 1458

Bravo AF: 0.132

Asia WGS AF: 0.0300 AC: 106 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs11045787; hg19: chr12-21300002;