chr12-21337447-A-G

Variant names:

• chr12-21337447-A-G
• rs2306231
• ENST00000307378.10:c.-62-2738T>C

Variant summary

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

The ENST00000307378.10(SLCO1A2):​c.-62-2738T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,742 control chromosomes in the GnomAD database, including 11,288 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 0.37 (11288 hom., cov: 32)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 8 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 (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1A2	NM_001386878.1	c.-62-2738T>C		intron_variant	Intron 1 of 14		NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-2743T>C		intron_variant	Intron 3 of 16		NP_001373810.1
SLCO1A2	NM_001386882.2	c.-62-2738T>C		intron_variant	Intron 1 of 14		NP_001373811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-62-2738T>C		intron_variant	Intron 2 of 15	1		ENSP00000305974.6
SLCO1A2	ENST00000453443.5	c.-62-2738T>C		intron_variant	Intron 1 of 4	3		ENSP00000409314.1
SLCO1A2	ENST00000450590.5	c.-57-2743T>C		intron_variant	Intron 1 of 3	4		ENSP00000407462.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56499 AN: 151624 Hom.: 11263 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56566 AN: 151742 Hom.: 11288 Cov.: 32 AF XY: 0.370 AC XY: 27473 AN XY: 74164

African (AFR) AF: 0.523 AC: 21633 AN: 41374

American (AMR) AF: 0.260 AC: 3962 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3460

East Asian (EAS) AF: 0.350 AC: 1795 AN: 5122

South Asian (SAS) AF: 0.312 AC: 1502 AN: 4818

European-Finnish (FIN) AF: 0.319 AC: 3370 AN: 10574

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21677 AN: 67872

Other (OTH) AF: 0.365 AC: 766 AN: 2100

Alfa AF: 0.332 Hom.: 10924

Bravo AF: 0.374

Asia WGS AF: 0.333 AC: 1158 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.55
PhyloP100		0.12
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: rs2306231; hg19: chr12-21490381;