rs5484

Variant names:

• chr12-21378503-C-T
• rs5484
• NM_000415.3:c.*77C>T

Variant summary

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

The ENST00000240652.8(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 ENST00000240652.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000240652.8. 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
	IAPP	NM_000415.3	MANE Select	c.*77C>T		3_prime_UTR	Exon 3 of 3	NP_000406.1
	IAPP	NM_001329201.2		c.*77C>T		3_prime_UTR	Exon 3 of 3	NP_001316130.1
	SLCO1A2	NM_001386878.1		c.-63+24916G>A		intron	N/A	NP_001373807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IAPP	ENST00000240652.8	TSL:1 MANE Select	c.*77C>T		3_prime_UTR	Exon 3 of 3	ENSP00000240652.3
	SLCO1A2	ENST00000307378.10	TSL:1	c.-189-3978G>A		intron	N/A	ENSP00000305974.6
	IAPP	ENST00000535428.1	TSL:3	c.*77C>T		3_prime_UTR	Exon 3 of 3	ENSP00000437559.1

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

African (AFR) AF: 0.178 AC: 4404 AN: 24774

American (AMR) AF: 0.0948 AC: 4114 AN: 43384

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5215 AN: 23406

East Asian (EAS) AF: 0.0689 AC: 2575 AN: 37348

South Asian (SAS) AF: 0.149 AC: 11393 AN: 76350

European-Finnish (FIN) AF: 0.160 AC: 8156 AN: 50956

Middle Eastern (MID) AF: 0.183 AC: 885 AN: 4838

European-Non Finnish (NFE) AF: 0.182 AC: 131876 AN: 724276

Other (OTH) AF: 0.175 AC: 8125 AN: 46362

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

African (AFR) AF: 0.177 AC: 7367 AN: 41510

American (AMR) AF: 0.135 AC: 2058 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3472

East Asian (EAS) AF: 0.0608 AC: 314 AN: 5166

South Asian (SAS) AF: 0.148 AC: 714 AN: 4814

European-Finnish (FIN) AF: 0.145 AC: 1528 AN: 10564

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12415 AN: 67968

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.179 Hom.: 9878

Bravo AF: 0.169

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.63
PhyloP100		0.96
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: rs5484; hg19: chr12-21531437; COSMIC: COSV53713457; COSMIC: COSV53713457;