12-21019310-A-G

Variant names:

• chr12-21019310-A-G
• rs201101377
• ENST00000540229.1:c.1866-48009A>G

Variant summary

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

The NM_001371097.1(SLCO1B3-SLCO1B7):​c.1866-48009A>G variant causes a intron change. The variant allele was found at a frequency of 0.00011 in 1,613,580 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 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: SLCO1B3-SLCO1B7 NM_001371097.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06525108).

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.1866-48009A>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.1866-48009A>G		intron	N/A	ENSP00000441269.1
	SLCO1B3-SLCO1B7	ENST00000381541.7	TSL:2	c.360-2151A>G		intron	N/A	ENSP00000370952.3	F5H094-1
	SLCO1B7	ENST00000648739.1		n.289A>G		non_coding_transcript_exon	Exon 3 of 14

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 34 AN: 251204 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000112 AC: 163 AN: 1461382 Hom.: 0 Cov.: 30 AF XY: 0.000127 AC XY: 92 AN XY: 727000

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00329 AC: 86 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111748

Other (OTH) AF: 0.000364 AC: 22 AN: 60366

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		6.8
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.023	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.50
MVP		0.25
MPC		0.028
ClinPred		0.50	T
GERP RS		3.3
Varity_R		0.27
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201101377; hg19: chr12-21172244;