rs1867931197

Variant names:

• chr12-21023198-A-G
• rs1867931197
• ENST00000540229.1:c.1866-44121A>G

Variant summary

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

The NM_001371097.1(SLCO1B3-SLCO1B7):​c.1866-44121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,128 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLCO1B3-SLCO1B7 NM_001371097.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.764
• 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=0.21160382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371097.1. 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.1866-44121A>G		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.1866-44121A>G		intron	N/A	ENSP00000441269.1
	SLCO1B3-SLCO1B7	ENST00000381541.7	TSL:2	c.638A>G	p.Asn213Ser	missense	Exon 6 of 14	ENSP00000370952.3	F5H094-1
	SLCO1B7	ENST00000648739.1		n.638A>G		non_coding_transcript_exon	Exon 6 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459128 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725838

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

African (AFR) AF: 0.0000300 AC: 1 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110502

Other (OTH) AF: 0.00 AC: 0 AN: 60288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.083
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.1
DANN	Benign	0.84
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.76
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.092
Sift	Benign	0.071	T
Sift4G	Benign	0.062	T
Polyphen		0.21	B
Vest4		0.037
MutPred		0.47		Gain of catalytic residue at N213 (P = 0)
MVP		0.28
MPC		0.0069
ClinPred		0.41	T
GERP RS		1.3
Varity_R		0.089
gMVP		0.26
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1867931197; hg19: chr12-21176132;