ENST00000540229.1:c.1866-45745T>C

Variant names:

• chr12-21021574-T-C
• rs1469410899
• ENST00000540229.1:c.1866-45745T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000540229.1(SLCO1B3-SLCO1B7):​c.1866-45745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,521,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SLCO1B3-SLCO1B7 ENST00000540229.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.603
• Publications: 0 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]

LOC124902894 (HGNC:):

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072292835).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3-SLCO1B7	NM_001371097.1		c.1866-45745T>C		intron	N/A	NP_001358026.1	A0A0A6YYJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1866-45745T>C		intron	N/A	ENSP00000441269.1
	SLCO1B3-SLCO1B7	ENST00000381541.7	TSL:2	c.473T>C	p.Ile158Thr	missense	Exon 4 of 14	ENSP00000370952.3	F5H094-1
	SLCO1B7	ENST00000648739.1		n.473T>C		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151942 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000292 AC: 4 AN: 1369866 Hom.: 0 Cov.: 26 AF XY: 0.00000293 AC XY: 2 AN XY: 681834

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29972

American (AMR) AF: 0.00 AC: 0 AN: 33884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 37636

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 77188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1052618

Other (OTH) AF: 0.0000175 AC: 1 AN: 56986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0477904), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151942 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74192

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67930

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.87
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.082	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.60
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.083
Sift	Benign	0.057	T
Sift4G	Benign	0.61	T
Polyphen		0.0030	B
Vest4		0.018
MutPred		0.44		Gain of catalytic residue at R160 (P = 0.0103)
MVP		0.061
MPC		0.0057
ClinPred		0.22	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1469410899; hg19: chr12-21174508;