rs5484

Positions:

• chr12-21378503-C-T

Variant summary

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

The NM_000415.3(IAPP):​c.*77C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,183,784 control chromosomes in the GnomAD database, including 18,281 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 0.17 (2274 hom., cov: 32)
  • Exomes 𝑓: 0.17 (16007 hom.)
• Consequence: IAPP NM_000415.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

Genes affected

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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IAPP	NM_000415.3	c.*77C>T		3_prime_UTR_variant	3/3	ENST00000240652.8	NP_000406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IAPP	ENST00000240652.8	c.*77C>T		3_prime_UTR_variant	3/3	1	NM_000415.3	ENSP00000240652	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25872 AN: 151972 Hom.: 2267 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.171 AC: 176743 AN: 1031694 Hom.: 16007 Cov.: 14 AF XY: 0.172 AC XY: 91261 AN XY: 531952

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.0948

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.0689

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.170 AC: 25894 AN: 152090 Hom.: 2274 Cov.: 32 AF XY: 0.166 AC XY: 12361 AN XY: 74340

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.178

Alfa AF: 0.181 Hom.: 4911

Bravo AF: 0.169

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.63

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: rs5484; hg19: chr12-21531437; COSMIC: COSV53713457; COSMIC: COSV53713457;