rs2045938

Positions:

• chr12-21367418-G-A
• chr12-21367418-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IAPP	NM_001329201.2	c.-15-5919G>A		intron_variant			NP_001316130.1
SLCO1A2	NM_001386878.1	c.-62-32709C>T		intron_variant			NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-32714C>T		intron_variant			NP_001373810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-63+6981C>T		intron_variant		1		ENSP00000305974	P1
SLCO1A2	ENST00000413682.5	c.-311-32714C>T		intron_variant		4		ENSP00000403638
SLCO1A2	ENST00000416627.1	c.-63+6981C>T		intron_variant		3		ENSP00000392124

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

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.326

Alfa AF: 0.286 Hom.: 8506

Bravo AF: 0.315

Asia WGS AF: 0.386 AC: 1343 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.24

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: rs2045938; hg19: chr12-21520352;