chr12-21172413-G-A

Variant names:

• chr12-21172413-G-A
• rs7295464
• NM_006446.5:c.85-237G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006446.5(SLCO1B1):​c.85-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,282 control chromosomes in the GnomAD database, including 60,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60473 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.408
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-21172413-G-A is Benign according to our data. Variant chr12-21172413-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.85-237G>A		intron	N/A	NP_006437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.85-237G>A		intron	N/A	ENSP00000256958.2	Q9Y6L6
	SLCO1B1	ENST00000870182.1		c.85-237G>A		intron	N/A	ENSP00000540241.1
	SLCO1B1	ENST00000870184.1		c.85-237G>A		intron	N/A	ENSP00000540243.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135523 AN: 152164 Hom.: 60435 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.891 AC: 135616 AN: 152282 Hom.: 60473 Cov.: 33 AF XY: 0.893 AC XY: 66487 AN XY: 74452

African (AFR) AF: 0.866 AC: 35995 AN: 41548

American (AMR) AF: 0.897 AC: 13723 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3256 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5180 AN: 5186

South Asian (SAS) AF: 0.966 AC: 4663 AN: 4826

European-Finnish (FIN) AF: 0.886 AC: 9401 AN: 10608

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60436 AN: 68022

Other (OTH) AF: 0.895 AC: 1892 AN: 2114

Alfa AF: 0.884 Hom.: 8971

Bravo AF: 0.890

Asia WGS AF: 0.974 AC: 3384 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.23
PhyloP100		-0.41
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: rs7295464; hg19: chr12-21325347;