rs4149057

Variant names:

• chr12-21178665-T-C
• rs4149057
• NM_006446.5:c.571T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21178665-T-C
• chr12-21178665-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006446.5(SLCO1B1):​c.571T>C​(p.Leu191Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,605,080 control chromosomes in the GnomAD database, including 277,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (19247 hom., cov: 32)
  • Exomes 𝑓: 0.59 (258238 hom.)
• Consequence: SLCO1B1 NM_006446.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.712
• Publications: 66 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-21178665-T-C is Benign according to our data. Variant chr12-21178665-T-C is described in ClinVar as Benign. ClinVar VariationId is 259984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.712 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.571T>C	p.Leu191Leu	synonymous	Exon 6 of 15	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.571T>C	p.Leu191Leu	synonymous	Exon 6 of 15	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.571T>C	p.Leu191Leu	synonymous	Exon 7 of 16	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.571T>C	p.Leu191Leu	synonymous	Exon 7 of 16	ENSP00000540243.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71378 AN: 151912 Hom.: 19248 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.484

GnomAD2 exomes AF: 0.530 AC: 133096 AN: 251042 AF XY: 0.541

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.249

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.588 AC: 854584 AN: 1453050 Hom.: 258238 Cov.: 32 AF XY: 0.587 AC XY: 424888 AN XY: 723466

African (AFR) AF: 0.182 AC: 6044 AN: 33284

American (AMR) AF: 0.523 AC: 23360 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 16262 AN: 26062

East Asian (EAS) AF: 0.294 AC: 11633 AN: 39588

South Asian (SAS) AF: 0.526 AC: 45329 AN: 86132

European-Finnish (FIN) AF: 0.519 AC: 27735 AN: 53406

Middle Eastern (MID) AF: 0.547 AC: 3133 AN: 5728

European-Non Finnish (NFE) AF: 0.623 AC: 687927 AN: 1104040

Other (OTH) AF: 0.552 AC: 33161 AN: 60118

GnomAD4 genome AF: 0.470 AC: 71384 AN: 152030 Hom.: 19247 Cov.: 32 AF XY: 0.464 AC XY: 34466 AN XY: 74310

African (AFR) AF: 0.204 AC: 8474 AN: 41506

American (AMR) AF: 0.518 AC: 7911 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2213 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1321 AN: 5172

South Asian (SAS) AF: 0.488 AC: 2355 AN: 4824

European-Finnish (FIN) AF: 0.511 AC: 5396 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41991 AN: 67934

Other (OTH) AF: 0.485 AC: 1020 AN: 2104

Alfa AF: 0.564 Hom.: 78242

Bravo AF: 0.460

Asia WGS AF: 0.347 AC: 1203 AN: 3474

EpiCase AF: 0.617

EpiControl AF: 0.622

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Rotor syndrome (4)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	SLCO1B1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.6
DANN	Benign	0.25
PhyloP100		-0.71
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: rs4149057; hg19: chr12-21331599; COSMIC: COSV57008088; COSMIC: COSV57008088;