rs2900478

Positions:

• chr12-21215863-T-A

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1498-1256T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,114 control chromosomes in the GnomAD database, including 1,586 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 (1586 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1498-1256T>A		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1498-1256T>A		intron_variant		1	NM_006446.5	ENSP00000256958	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19324 AN: 151996 Hom.: 1587 Cov.: 31

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.127 AC: 19319 AN: 152114 Hom.: 1586 Cov.: 31 AF XY: 0.131 AC XY: 9738 AN XY: 74368

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.142

Alfa AF: 0.156 Hom.: 261

Bravo AF: 0.117

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.31

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: rs2900478; hg19: chr12-21368797;