chr12-21304500-T-G

Variant names:

• chr12-21304500-T-G
• rs11568563
• NM_001386879.1:c.516A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386879.1(SLCO1A2):​c.516A>C​(p.Glu172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 1,611,832 control chromosomes in the GnomAD database, including 2,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.043 (200 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2517 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 67 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068627).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386879.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	NM_001386879.1	MANE Select	c.516A>C	p.Glu172Asp	missense	Exon 6 of 15	NP_001373808.1
	SLCO1A2	NM_001386878.1		c.516A>C	p.Glu172Asp	missense	Exon 6 of 15	NP_001373807.1
	SLCO1A2	NM_001386880.1		c.516A>C	p.Glu172Asp	missense	Exon 6 of 15	NP_001373809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	ENST00000683939.1	MANE Select	c.516A>C	p.Glu172Asp	missense	Exon 6 of 15	ENSP00000508235.1
	SLCO1A2	ENST00000307378.10	TSL:1	c.516A>C	p.Glu172Asp	missense	Exon 7 of 16	ENSP00000305974.6
	SLCO1A2	ENST00000544020.5	TSL:1	n.*95A>C		non_coding_transcript_exon	Exon 5 of 14	ENSP00000440154.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6546 AN: 152058 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0450 AC: 11305 AN: 251144 AF XY: 0.0454

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.0343

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0795

Gnomad NFE exome AF: 0.0622

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0553 AC: 80721 AN: 1459658 Hom.: 2517 Cov.: 30 AF XY: 0.0544 AC XY: 39499 AN XY: 726200

African (AFR) AF: 0.0167 AC: 558 AN: 33440

American (AMR) AF: 0.0296 AC: 1324 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 888 AN: 26110

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.0211 AC: 1818 AN: 86184

European-Finnish (FIN) AF: 0.0821 AC: 4383 AN: 53360

Middle Eastern (MID) AF: 0.0127 AC: 73 AN: 5758

European-Non Finnish (NFE) AF: 0.0620 AC: 68821 AN: 1110150

Other (OTH) AF: 0.0473 AC: 2849 AN: 60282

GnomAD4 genome AF: 0.0430 AC: 6544 AN: 152174 Hom.: 200 Cov.: 32 AF XY: 0.0425 AC XY: 3162 AN XY: 74376

African (AFR) AF: 0.0174 AC: 722 AN: 41530

American (AMR) AF: 0.0406 AC: 620 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4822

European-Finnish (FIN) AF: 0.0743 AC: 787 AN: 10590

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0596 AC: 4049 AN: 67990

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0521 Hom.: 1007

Bravo AF: 0.0402

TwinsUK AF: 0.0626 AC: 232

ALSPAC AF: 0.0597 AC: 230

ESP6500AA AF: 0.0186 AC: 82

ESP6500EA AF: 0.0558 AC: 480

ExAC AF: 0.0455 AC: 5520

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.0524

EpiControl AF: 0.0527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		2.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.36		Gain of catalytic residue at L176 (P = 0)
MPC		0.24
ClinPred		0.058	T
GERP RS		3.6
Varity_R		0.86
gMVP		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11568563; hg19: chr12-21457434; COSMIC: COSV56600006; COSMIC: COSV56600006;