12-21306942-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001386879.1(SLCO1A2):c.382A>T(p.Asn128Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,300 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0056 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (7 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00825569).
• BP6: Variant 12-21306942-T-A is Benign according to our data. Variant chr12-21306942-T-A is described in ClinVar as [Benign]. Clinvar id is 786223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00562 (855/152226) while in subpopulation AFR AF= 0.0193 (801/41572). AF 95% confidence interval is 0.0182. There are 9 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1A2	NM_001386879.1	c.382A>T	p.Asn128Tyr	missense_variant	5/15	ENST00000683939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1A2	ENST00000683939.1	c.382A>T	p.Asn128Tyr	missense_variant	5/15		NM_001386879.1	P1

Frequencies

GnomAD3 genomes AF: 0.00561 AC: 854 AN: 152108 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00168 AC: 423 AN: 251292 Hom.: 8 AF XY: 0.00126 AC XY: 171 AN XY: 135804

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000673 AC: 983 AN: 1461074 Hom.: 7 Cov.: 30 AF XY: 0.000619 AC XY: 450 AN XY: 726800

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00562 AC: 855 AN: 152226 Hom.: 9 Cov.: 32 AF XY: 0.00543 AC XY: 404 AN XY: 74428

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000996 Hom.: 2

Bravo AF: 0.00612

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0163 AC: 72

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00203 AC: 246

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.64	T;T;T
MetaRNN	Benign	0.0083	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.2	M;.;.
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.30	T;T;D
Sift4G	Benign	0.23	T;.;.
Polyphen		0.94	P;.;.
Vest4		0.47
MVP		0.52
MPC		0.19
ClinPred		0.069	T
GERP RS		3.1
Varity_R		0.23
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs11568567; hg19: chr12-21459876;