12-20965522-T-C

Variant names:

• chr12-20965522-T-C
• rs10770763
• ENST00000540229.1:c.1865+64055T>C

Variant summary

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

The ENST00000540229.1(SLCO1B3-SLCO1B7):​c.1865+64055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,698 control chromosomes in the GnomAD database, including 20,862 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 0.48 (20862 hom., cov: 32)
• Consequence: SLCO1B3-SLCO1B7 ENST00000540229.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 2 publications found

Genes affected

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]

SLCO1B7 (HGNC:32934): (solute carrier organic anion transporter family member 1B7 (putative)) Predicted to enable bile acid transmembrane transporter activity and sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in bile acid and bile salt transport and sodium-independent organic anion transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO1B7 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LOC124902894 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540229.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3-SLCO1B7	NM_001371097.1		c.1865+64055T>C		intron	N/A	NP_001358026.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1865+64055T>C		intron	N/A	ENSP00000441269.1
	SLCO1B3-SLCO1B7	ENST00000381541.7	TSL:2	c.360-55939T>C		intron	N/A	ENSP00000370952.3
	SLCO1B7	ENST00000648739.1		n.84+2671T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72732 AN: 151580 Hom.: 20854 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.480 AC: 72745 AN: 151698 Hom.: 20862 Cov.: 32 AF XY: 0.484 AC XY: 35870 AN XY: 74102

African (AFR) AF: 0.147 AC: 6115 AN: 41486

American (AMR) AF: 0.532 AC: 8076 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1820 AN: 3466

East Asian (EAS) AF: 0.554 AC: 2845 AN: 5134

South Asian (SAS) AF: 0.742 AC: 3579 AN: 4826

European-Finnish (FIN) AF: 0.578 AC: 6096 AN: 10550

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42486 AN: 67758

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.529 Hom.: 4129

Bravo AF: 0.461

Asia WGS AF: 0.604 AC: 2091 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.92
PhyloP100		0.15
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: rs10770763; hg19: chr12-21118456;