rs10743397

Variant names:

• chr12-20834422-G-A
• rs10743397
• NM_019844.4:c.84+18600G>A

Variant summary

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

The NM_019844.4(SLCO1B3):​c.84+18600G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 144,732 control chromosomes in the GnomAD database, including 17,044 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 0.46 (17044 hom., cov: 27)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 1 publications found

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:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. 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
	SLCO1B3	NM_019844.4	MANE Select	c.84+18600G>A		intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.84+18600G>A		intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.-1+11749G>A		intron	N/A	NP_001336849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.84+18600G>A		intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.84+18600G>A		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.84+18600G>A		intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 66101 AN: 144740 Hom.: 17057 Cov.: 27

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.496

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.457 AC: 66076 AN: 144732 Hom.: 17044 Cov.: 27 AF XY: 0.464 AC XY: 32513 AN XY: 70082

African (AFR) AF: 0.204 AC: 8132 AN: 39916

American (AMR) AF: 0.574 AC: 8153 AN: 14192

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2043 AN: 3440

East Asian (EAS) AF: 0.624 AC: 3105 AN: 4976

South Asian (SAS) AF: 0.642 AC: 2964 AN: 4618

European-Finnish (FIN) AF: 0.549 AC: 4336 AN: 7902

Middle Eastern (MID) AF: 0.482 AC: 107 AN: 222

European-Non Finnish (NFE) AF: 0.539 AC: 35906 AN: 66608

Other (OTH) AF: 0.456 AC: 897 AN: 1968

Alfa AF: 0.480 Hom.: 2309

Bravo AF: 0.449

Asia WGS AF: 0.579 AC: 1913 AN: 3308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.17
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: rs10743397; hg19: chr12-20987356;