12-20915981-C-T

Variant names:

• chr12-20915981-C-T
• rs78862986
• NM_019844.4:c.1866-23C>T

Variant summary

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

The NM_019844.4(SLCO1B3):​c.1866-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,544,480 control chromosomes in the GnomAD database, including 292 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 0.0098 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (255 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• 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]

LOC124902894 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.0915 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.1866-23C>T		intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.1865+14514C>T		intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.1782-23C>T		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.1866-23C>T		intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1865+14514C>T		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.1866-23C>T		intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.00976 AC: 1483 AN: 151992 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.0151 AC: 3349 AN: 222334 AF XY: 0.0139

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.00127

Gnomad EAS exome AF: 0.0978

Gnomad FIN exome AF: 0.000498

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.00951

GnomAD4 exome AF: 0.00516 AC: 7187 AN: 1392370 Hom.: 255 Cov.: 27 AF XY: 0.00534 AC XY: 3697 AN XY: 692378

African (AFR) AF: 0.0134 AC: 410 AN: 30522

American (AMR) AF: 0.0335 AC: 1179 AN: 35228

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 33 AN: 23858

East Asian (EAS) AF: 0.0860 AC: 3354 AN: 39004

South Asian (SAS) AF: 0.0164 AC: 1296 AN: 79092

European-Finnish (FIN) AF: 0.000539 AC: 28 AN: 51962

Middle Eastern (MID) AF: 0.00243 AC: 12 AN: 4932

European-Non Finnish (NFE) AF: 0.000201 AC: 215 AN: 1070306

Other (OTH) AF: 0.0115 AC: 660 AN: 57466

GnomAD4 genome AF: 0.00982 AC: 1494 AN: 152110 Hom.: 37 Cov.: 32 AF XY: 0.0105 AC XY: 778 AN XY: 74354

African (AFR) AF: 0.0130 AC: 541 AN: 41494

American (AMR) AF: 0.0179 AC: 273 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.0986 AC: 510 AN: 5174

South Asian (SAS) AF: 0.0210 AC: 101 AN: 4818

European-Finnish (FIN) AF: 0.000568 AC: 6 AN: 10568

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67996

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.00493 Hom.: 3

Bravo AF: 0.0120

Asia WGS AF: 0.0650 AC: 227 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs78862986; hg19: chr12-21068915; COSMIC: COSV53938537;