rs9658638

Positions:

• chr14-92923090-C-T

Variant summary

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

The XM_011536370.3(CHGA):​c.-189+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 296,680 control chromosomes in the GnomAD database, including 4,374 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 (2310 hom., cov: 33)
  • Exomes 𝑓: 0.16 (2064 hom.)
• Consequence: CHGA XM_011536370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

Genes affected

CHGA (HGNC:1929): (chromogranin A) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	XM_011536370.3	c.-189+78C>T		intron_variant			XP_011534672.1
		n.92923090C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25947 AN: 152126 Hom.: 2303 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.163 AC: 23557 AN: 144436 Hom.: 2064 Cov.: 1 AF XY: 0.163 AC XY: 12018 AN XY: 73940

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0988

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.171 AC: 25975 AN: 152244 Hom.: 2310 Cov.: 33 AF XY: 0.174 AC XY: 12937 AN XY: 74458

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.158

Alfa AF: 0.158 Hom.: 625

Bravo AF: 0.158

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.98

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: rs9658638; hg19: chr14-93389435; COSMIC: COSV53664722; COSMIC: COSV53664722;