chr3-187669043-T-C

Variant names:

• chr3-187669043-T-C
• rs4988514
• NM_001048.4:c.*22A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SST	NM_001048.4	MANE Select	c.*22A>G		3_prime_UTR	Exon 2 of 2	NP_001039.1	P61278

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SST	ENST00000287641.4	TSL:1 MANE Select	c.*22A>G		3_prime_UTR	Exon 2 of 2	ENSP00000287641.3	P61278

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

GnomAD2 exomes AF: 0.109 AC: 27506 AN: 251394 AF XY: 0.104

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 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

African (AFR) AF: 0.150 AC: 5012 AN: 33458

American (AMR) AF: 0.189 AC: 8450 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3072 AN: 26126

East Asian (EAS) AF: 0.0609 AC: 2416 AN: 39694

South Asian (SAS) AF: 0.0767 AC: 6612 AN: 86238

European-Finnish (FIN) AF: 0.142 AC: 7555 AN: 53330

Middle Eastern (MID) AF: 0.120 AC: 693 AN: 5760

European-Non Finnish (NFE) AF: 0.0860 AC: 95515 AN: 1110932

Other (OTH) AF: 0.0966 AC: 5828 AN: 60346

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

African (AFR) AF: 0.143 AC: 5925 AN: 41468

American (AMR) AF: 0.168 AC: 2558 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.0565 AC: 292 AN: 5168

South Asian (SAS) AF: 0.0738 AC: 355 AN: 4812

European-Finnish (FIN) AF: 0.156 AC: 1644 AN: 10540

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0890 AC: 6050 AN: 67988

Other (OTH) AF: 0.107 AC: 226 AN: 2108

Alfa AF: 0.103 Hom.: 1183

Bravo AF: 0.121

Asia WGS AF: 0.0880 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.33
PhyloP100		-0.65
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: rs4988514; hg19: chr3-187386831; COSMIC: COSV55030593;