12-21367418-G-A

Variant names:

• chr12-21367418-G-A
• rs2045938
• ENST00000307378.10:c.-63+6981C>T

Variant summary

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

The ENST00000307378.10(SLCO1A2):​c.-63+6981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,918 control chromosomes in the GnomAD database, including 8,219 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 0.32 (8219 hom., cov: 31)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 6 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]

IAPP (HGNC:5329): (islet amyloid polypeptide) This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307378.10. 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_001386878.1		c.-62-32709C>T		intron	N/A	NP_001373807.1
	SLCO1A2	NM_001386881.1		c.-57-32714C>T		intron	N/A	NP_001373810.1
	SLCO1A2	NM_134431.5		c.-63+6981C>T		intron	N/A	NP_602307.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	ENST00000307378.10	TSL:1	c.-63+6981C>T		intron	N/A	ENSP00000305974.6
	SLCO1A2	ENST00000453443.5	TSL:3	c.-62-32709C>T		intron	N/A	ENSP00000409314.1
	SLCO1A2	ENST00000450590.5	TSL:4	c.-57-32714C>T		intron	N/A	ENSP00000407462.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48994 AN: 151800 Hom.: 8208 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.323 AC: 49045 AN: 151918 Hom.: 8219 Cov.: 31 AF XY: 0.325 AC XY: 24116 AN XY: 74238

African (AFR) AF: 0.395 AC: 16360 AN: 41442

American (AMR) AF: 0.242 AC: 3692 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3462

East Asian (EAS) AF: 0.460 AC: 2373 AN: 5158

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4820

European-Finnish (FIN) AF: 0.349 AC: 3677 AN: 10544

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18882 AN: 67906

Other (OTH) AF: 0.326 AC: 689 AN: 2114

Alfa AF: 0.287 Hom.: 10891

Bravo AF: 0.315

Asia WGS AF: 0.386 AC: 1343 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.24
PhyloP100		-0.23
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: rs2045938; hg19: chr12-21520352;