rs4988514

chr3-187669043-T-C

Variant summary

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

The NM_001048.4(SST):c.*22A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 1,612,634 control chromosomes in the GnomAD database, including 7,878 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 0.12 (1096 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6782 hom.)
• Consequence: SST NM_001048.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

Genes affected

SST (HGNC:11329): (somatostatin) The hormone somatostatin has active 14 aa and 28 aa forms that are produced by alternate cleavage of the single preproprotein encoded by this gene. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled somatostatin receptors. This hormone is an important regulator of the endocrine system through its interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system and proliferation of both normal and tumorigenic cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SST	NM_001048.4	c.*22A>G		3_prime_UTR_variant	2/2	ENST00000287641.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SST	ENST00000287641.4	c.*22A>G		3_prime_UTR_variant	2/2	1	NM_001048.4	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17661 AN: 151908 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.109 AC: 27506 AN: 251394 Hom.: 1744 AF XY: 0.104 AC XY: 14186 AN XY: 135878

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0561

Gnomad SAS exome AF: 0.0749

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.0906

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0925 AC: 135153 AN: 1460608 Hom.: 6782 Cov.: 30 AF XY: 0.0919 AC XY: 66759 AN XY: 726710

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0767

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.0860

Gnomad4 OTH exome AF: 0.0966

GnomAD4 genome AF: 0.116 AC: 17670 AN: 152026 Hom.: 1096 Cov.: 32 AF XY: 0.119 AC XY: 8841 AN XY: 74294

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.107

Alfa AF: 0.100 Hom.: 865

Bravo AF: 0.121

Asia WGS AF: 0.0880 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.43
Dann	Benign	0.33

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: rs4988514; hg19: chr3-187386831; COSMIC: COSV55030593;