Genetic Variant SLCO1B3-SLCO1B7:c.1866-44079G>A (chr12-21023240-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371097.1(SLCO1B3-SLCO1B7):c.1866-44079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLCO1B3-SLCO1B7
NM_001371097.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.466

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902894	XM_047429949.1 link	c.539G>A	p.Gly180Glu	missense_variant	Exon 6 of 10		XP_047285905.1
SLCO1B3-SLCO1B7	NM_001371097.1 link	c.1866-44079G>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.1866-44079G>A		intron_variant	Intron 13 of 15	2	ENSP00000441269.1	A0A0A6YYJ9
SLCO1B3-SLCO1B7	ENST00000381541.7 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 6 of 14	2	ENSP00000370952.3	F5H094-1
SLCO1B7	ENST00000648739.1 link	n.680G>A		non_coding_transcript_exon_variant	Exon 6 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460518

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.539G>A (p.G180E) 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 539, causing the glycine (G) at amino acid position 180 to be replaced by a glutamic acid (E). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

.;T

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0060

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.5

.;H

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.99

.;D

Vest4

0.40

MutPred

0.70

Gain of catalytic residue at A223 (P = 0.0095);.;

MVP

0.36

MPC

0.027

ClinPred

0.98

GERP RS

-5.1

Varity_R

0.87

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over