12-21226698-A-G

Variant names:

• chr12-21226698-A-G
• rs7966613
• NM_006446.5:c.1865+1859A>G

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1865+1859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,894 control chromosomes in the GnomAD database, including 9,116 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 0.34 (9116 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.437 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.1865+1859A>G		intron	N/A	NP_006437.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.1865+1859A>G		intron	N/A	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51594 AN: 151778 Hom.: 9113 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.340 AC: 51622 AN: 151894 Hom.: 9116 Cov.: 31 AF XY: 0.344 AC XY: 25536 AN XY: 74224

African (AFR) AF: 0.297 AC: 12328 AN: 41444

American (AMR) AF: 0.298 AC: 4539 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2322 AN: 5134

South Asian (SAS) AF: 0.202 AC: 973 AN: 4810

European-Finnish (FIN) AF: 0.443 AC: 4670 AN: 10530

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24128 AN: 67946

Other (OTH) AF: 0.343 AC: 723 AN: 2110

Alfa AF: 0.347 Hom.: 29712

Bravo AF: 0.332

Asia WGS AF: 0.316 AC: 1097 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		-0.40
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: rs7966613; hg19: chr12-21379632;