rs2417940

Variant names:

• chr12-20864941-T-C
• rs2417940
• NM_019844.4:c.727+2087T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-20864941-T-C
• chr12-20864941-T-A
• chr12-20864941-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_019844.4(SLCO1B3):​c.727+2087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 151,900 control chromosomes in the GnomAD database, including 45,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.76 (45369 hom., cov: 31)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.41
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 12-20864941-T-C is Benign according to our data. Variant chr12-20864941-T-C is described in ClinVar as Benign. ClinVar VariationId is 810734.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 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.727+2087T>C		intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.727+2087T>C		intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.643+2087T>C		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.727+2087T>C		intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.727+2087T>C		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.727+2087T>C		intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115375 AN: 151782 Hom.: 45349 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.760 AC: 115443 AN: 151900 Hom.: 45369 Cov.: 31 AF XY: 0.759 AC XY: 56381 AN XY: 74250

African (AFR) AF: 0.539 AC: 22322 AN: 41410

American (AMR) AF: 0.838 AC: 12785 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3094 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4209 AN: 5150

South Asian (SAS) AF: 0.919 AC: 4423 AN: 4814

European-Finnish (FIN) AF: 0.747 AC: 7893 AN: 10572

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57971 AN: 67926

Other (OTH) AF: 0.811 AC: 1707 AN: 2104

Alfa AF: 0.815 Hom.: 95003

Bravo AF: 0.758

Asia WGS AF: 0.837 AC: 2910 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Gilbert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.38
PhyloP100		-2.4
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: rs2417940; hg19: chr12-21017875;