12-21372672-A-C

Position:

• chr12-21372672-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307378.10(SLCO1A2):​c.-63+1727T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,090 control chromosomes in the GnomAD database, including 15,123 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 0.44 (15123 hom., cov: 33)
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IAPP	NM_001329201.2	c.-15-665A>C		intron_variant			NP_001316130.1
SLCO1A2	NM_001386878.1	c.-63+30747T>G		intron_variant			NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-37968T>G		intron_variant			NP_001373810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-63+1727T>G		intron_variant		1		ENSP00000305974	P1
SLCO1A2	ENST00000413682.5	c.-311-37968T>G		intron_variant		4		ENSP00000403638
SLCO1A2	ENST00000416627.1	c.-63+1727T>G		intron_variant		3		ENSP00000392124

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67308 AN: 151972 Hom.: 15118 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.443 AC: 67339 AN: 152090 Hom.: 15123 Cov.: 33 AF XY: 0.435 AC XY: 32373 AN XY: 74346

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.449

Alfa AF: 0.454 Hom.: 21127

Bravo AF: 0.454

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.67

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: rs7137767; hg19: chr12-21525606;