12-21021561-C-T

Variant names:

• chr12-21021561-C-T
• ENST00000540229.1:c.1866-45758C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001371097.1(SLCO1B3-SLCO1B7):​c.1866-45758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLCO1B3-SLCO1B7 NM_001371097.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03536412).
• BP6: Variant 12-21021561-C-T is Benign according to our data. Variant chr12-21021561-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3798473.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1866-45758C>T		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.1866-45758C>T		intron	N/A	ENSP00000441269.1
	SLCO1B3-SLCO1B7	ENST00000381541.7	TSL:2	c.460C>T	p.Pro154Ser	missense	Exon 4 of 14	ENSP00000370952.3	F5H094-1
	SLCO1B7	ENST00000648739.1		n.460C>T		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1397216 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 695234

African (AFR) AF: 0.00 AC: 0 AN: 31162

American (AMR) AF: 0.00 AC: 0 AN: 37866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24934

East Asian (EAS) AF: 0.00 AC: 0 AN: 38134

South Asian (SAS) AF: 0.00 AC: 0 AN: 79692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069696

Other (OTH) AF: 0.00 AC: 0 AN: 58040

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.059
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.2
DANN	Benign	0.65
DEOGEN2	Benign	0.00053	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00069	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.062
PROVEAN	Benign	1.8	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.36		Gain of catalytic residue at E159 (P = 0.0805)
MVP		0.072
MPC		0.0061
ClinPred		0.11	T
GERP RS		-1.6
Varity_R		0.018
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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

hg19: chr12-21174495;