rs11045818

Variant names:

• chr12-21176827-G-A
• rs11045818
• NM_006446.5:c.411G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-21176827-G-A
• chr12-21176827-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006446.5(SLCO1B1):​c.411G>A​(p.Ser137Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,505,436 control chromosomes in the GnomAD database, including 11,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1195 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10719 hom.)
• Consequence: SLCO1B1 NM_006446.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.153
• Publications: 38 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

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-21176827-G-A is Benign according to our data. Variant chr12-21176827-G-A is described in ClinVar as Benign. ClinVar VariationId is 307936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 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.411G>A	p.Ser137Ser	synonymous	Exon 5 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.411G>A	p.Ser137Ser	synonymous	Exon 5 of 15	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.411G>A	p.Ser137Ser	synonymous	Exon 6 of 16	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.411G>A	p.Ser137Ser	synonymous	Exon 6 of 16	ENSP00000540243.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16488 AN: 151934 Hom.: 1196 Cov.: 33

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.111 AC: 27884 AN: 250236 AF XY: 0.113

Gnomad AFR exome AF: 0.0355

Gnomad AMR exome AF: 0.0683

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.114 AC: 153953 AN: 1353384 Hom.: 10719 Cov.: 26 AF XY: 0.112 AC XY: 75928 AN XY: 676984

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0263 AC: 840 AN: 31906

American (AMR) AF: 0.0648 AC: 2860 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4385 AN: 24624

East Asian (EAS) AF: 0.000255 AC: 10 AN: 39268

South Asian (SAS) AF: 0.0414 AC: 3520 AN: 85002

European-Finnish (FIN) AF: 0.0928 AC: 4771 AN: 51432

Middle Eastern (MID) AF: 0.0894 AC: 490 AN: 5484

European-Non Finnish (NFE) AF: 0.129 AC: 131107 AN: 1015038

Other (OTH) AF: 0.106 AC: 5970 AN: 56512

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.108 AC: 16480 AN: 152052 Hom.: 1195 Cov.: 33 AF XY: 0.104 AC XY: 7697 AN XY: 74340

African (AFR) AF: 0.0374 AC: 1554 AN: 41530

American (AMR) AF: 0.0961 AC: 1467 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4814

European-Finnish (FIN) AF: 0.104 AC: 1096 AN: 10570

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10785 AN: 67918

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.140 Hom.: 4102

Bravo AF: 0.108

Asia WGS AF: 0.0190 AC: 67 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		0.15
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: rs11045818; hg19: chr12-21329761; COSMIC: COSV108750638;