12-21023211-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001371097.1(SLCO1B3-SLCO1B7):c.1866-44108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,612,172 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 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

SLCO1B3-SLCO1B7
NM_001371097.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159

Variant links:

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]

SLCO1B3-SLCO1B7 links:

LOC124902894 (HGNC:):

LOC124902894 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058726043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902894	XM_047429949.1 link	c.510G>A	p.Met170Ile	missense_variant	Exon 6 of 10		XP_047285905.1
SLCO1B3-SLCO1B7	NM_001371097.1 link	c.1866-44108G>A		intron_variant	Intron 13 of 15		NP_001358026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SLCO1B3-SLCO1B7	ENST00000540229.1 link	c.1866-44108G>A		intron_variant	Intron 13 of 15	2	ENSP00000441269.1	A0A0A6YYJ9
SLCO1B3-SLCO1B7	ENST00000381541.7 link	c.651G>A	p.Met217Ile	missense_variant	Exon 6 of 14	2	ENSP00000370952.3	F5H094-1
SLCO1B7	ENST00000648739.1 link	n.651G>A		non_coding_transcript_exon_variant	Exon 6 of 14

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

248724

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000316

AC:

461

AN:

1460092

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

233

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000389

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000132

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000694

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000383

EpiControl

AF:

0.000239

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.510G>A (p.M170I) alteration is located in exon 5 (coding exon 5) of the SLCO1B7 gene. This alteration results from a G to A substitution at nucleotide position 510, causing the methionine (M) at amino acid position 170 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0041

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.12

Sift

Benign

0.65

T;T

Sift4G

Benign

0.92

T;T

Polyphen

0.017

.;B

Vest4

0.14

MutPred

0.54

Gain of catalytic residue at T218 (P = 0);.;

MVP

0.099

MPC

0.0061

ClinPred

0.062

GERP RS

2.5

Varity_R

0.37

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over