chr12-21239860-A-G

Variant names:

• chr12-21239860-A-G
• rs11045892
• XR_007063239.1:n.87-5561T>C

Variant summary

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

The XR_007063239.1(LOC124902895):​n.87-5561T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,232 control chromosomes in the GnomAD database, including 1,661 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 0.13 (1661 hom., cov: 33)
• Consequence: LOC124902895 XR_007063239.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 6 publications found

Genes affected

LOC124902895 (HGNC:):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000256958.3. 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.*671A>G		downstream_gene	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.*671A>G		downstream_gene	N/A	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20314 AN: 152114 Hom.: 1664 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.133 AC: 20313 AN: 152232 Hom.: 1661 Cov.: 33 AF XY: 0.128 AC XY: 9515 AN XY: 74444

African (AFR) AF: 0.0739 AC: 3071 AN: 41538

American (AMR) AF: 0.110 AC: 1679 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3468

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0775 AC: 374 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1290 AN: 10600

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12380 AN: 67996

Other (OTH) AF: 0.135 AC: 286 AN: 2114

Alfa AF: 0.166 Hom.: 2842

Bravo AF: 0.133

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.43
PhyloP100		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11045892; hg19: chr12-21392794;