chr12-21219410-A-G

Variant names:

• chr12-21219410-A-G
• rs11045872
• NM_006446.5:c.1682+2107A>G

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1682+2107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,158 control chromosomes in the GnomAD database, including 1,691 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 (1691 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1682+2107A>G		intron_variant	Intron 12 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1682+2107A>G		intron_variant	Intron 12 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20392 AN: 152040 Hom.: 1694 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.134 AC: 20387 AN: 152158 Hom.: 1691 Cov.: 32 AF XY: 0.129 AC XY: 9607 AN XY: 74398

African (AFR) AF: 0.0684 AC: 2838 AN: 41518

American (AMR) AF: 0.111 AC: 1700 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.113 AC: 544 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1308 AN: 10582

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12479 AN: 67988

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.153 Hom.: 3386

Bravo AF: 0.132

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.75
PhyloP100		0.097
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: rs11045872; hg19: chr12-21372344;