chr12-21224625-G-C

Variant names:

• chr12-21224625-G-C
• rs4149080
• NM_006446.5:c.1748-97G>C

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.1748-97G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 797,010 control chromosomes in the GnomAD database, including 16,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2982 hom., cov: 32)
  • Exomes 𝑓: 0.19 (13442 hom.)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.59
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-21224625-G-C is Benign according to our data. Variant chr12-21224625-G-C is described in ClinVar as Benign. ClinVar VariationId is 1295279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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.1748-97G>C		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.1748-97G>C		intron	N/A	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28193 AN: 151782 Hom.: 2979 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.188 AC: 121190 AN: 645110 Hom.: 13442 AF XY: 0.181 AC XY: 62942 AN XY: 347714

African (AFR) AF: 0.160 AC: 2618 AN: 16318

American (AMR) AF: 0.148 AC: 5041 AN: 34142

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3632 AN: 19144

East Asian (EAS) AF: 0.419 AC: 14667 AN: 34976

South Asian (SAS) AF: 0.0771 AC: 4848 AN: 62888

European-Finnish (FIN) AF: 0.304 AC: 14742 AN: 48558

Middle Eastern (MID) AF: 0.196 AC: 465 AN: 2368

European-Non Finnish (NFE) AF: 0.174 AC: 68466 AN: 394014

Other (OTH) AF: 0.205 AC: 6711 AN: 32702

GnomAD4 genome AF: 0.186 AC: 28213 AN: 151900 Hom.: 2982 Cov.: 32 AF XY: 0.196 AC XY: 14513 AN XY: 74224

African (AFR) AF: 0.158 AC: 6562 AN: 41456

American (AMR) AF: 0.180 AC: 2739 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2326 AN: 5154

South Asian (SAS) AF: 0.0880 AC: 424 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3414 AN: 10534

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11622 AN: 67894

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.181 Hom.: 348

Bravo AF: 0.176

Asia WGS AF: 0.259 AC: 897 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.045
DANN	Benign	0.54
PhyloP100		-2.6
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: rs4149080; hg19: chr12-21377559;