rs10841795

chr12-21334610-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386879.1(SLCO1A2):c.38T>C(p.Ile13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,608,460 control chromosomes in the GnomAD database, including 12,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.090 (868 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11160 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016459525).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1A2	NM_001386879.1	c.38T>C	p.Ile13Thr	missense_variant	2/15	ENST00000683939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1A2	ENST00000683939.1	c.38T>C	p.Ile13Thr	missense_variant	2/15		NM_001386879.1	P1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13758 AN: 151928 Hom.: 868 Cov.: 33

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.0975 AC: 24252 AN: 248762 Hom.: 1474 AF XY: 0.102 AC XY: 13730 AN XY: 134494

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.0593

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.000382

Gnomad SAS exome AF: 0.0705

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.118 AC: 172049 AN: 1456414 Hom.: 11160 Cov.: 30 AF XY: 0.118 AC XY: 85444 AN XY: 724670

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.0638

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.0698

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0904 AC: 13748 AN: 152046 Hom.: 868 Cov.: 33 AF XY: 0.0878 AC XY: 6525 AN XY: 74332

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.103

Alfa AF: 0.127 Hom.: 3391

Bravo AF: 0.0882

TwinsUK AF: 0.141 AC: 523

ALSPAC AF: 0.134 AC: 515

ESP6500AA AF: 0.0256 AC: 113

ESP6500EA AF: 0.136 AC: 1169

ExAC AF: 0.101 AC: 12278

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	15
Dann	Benign	0.52
DEOGEN2	Benign	0.026	T;.;.;.;.;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.69	T;T;T;T;T;T;T;.
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.60	N;N;N;N;N;N;N;D
REVEL	Benign	0.065
Sift	Benign	0.45	T;T;T;T;T;T;D;.
Sift4G	Benign	0.48	T;.;.;.;T;T;T;.
Polyphen		0.0020	B;.;.;.;.;.;.;.
Vest4		0.053
MPC		0.046
ClinPred		0.0087	T
GERP RS		3.7
Varity_R		0.065
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs10841795; hg19: chr12-21487544;