rs11045585

Positions:

• chr12-20892760-A-G
• chr12-20892760-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019844.4(SLCO1B3):​c.1683-5676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,162 control chromosomes in the GnomAD database, including 2,283 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 0.17 (2283 hom., cov: 32)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) 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 endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

SLCO1B3-SLCO1B7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1683-5676A>G		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1683-5676A>G		intron_variant			NP_001358026.1
SLCO1B3	NM_001349920.2	c.1599-5676A>G		intron_variant			NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1683-5676A>G		intron_variant		2	NM_019844.4	ENSP00000370956	P1
SLCO1B3	ENST00000261196.6	c.1683-5676A>G		intron_variant		1		ENSP00000261196	P1
SLCO1B3	ENST00000544370.1	c.1155-5676A>G		intron_variant		5		ENSP00000443225

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25366 AN: 152044 Hom.: 2280 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.167 AC: 25379 AN: 152162 Hom.: 2283 Cov.: 32 AF XY: 0.171 AC XY: 12703 AN XY: 74384

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0541

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.146

Alfa AF: 0.132 Hom.: 1972

Bravo AF: 0.161

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045585; hg19: chr12-21045694;