rs9658638

Variant names:

• chr14-92923090-C-T
• rs9658638
• ENST00000903321.1:c.-189+78C>T

Variant summary

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

The ENST00000903321.1(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 ENST00000903321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000903321.1. 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
	CHGA	NM_001275.4	MANE Select	c.-270C>T		upstream_gene	N/A	NP_001266.1	P10645
	CHGA	NM_001301690.2		c.-270C>T		upstream_gene	N/A	NP_001288619.1	G5E968

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGA	ENST00000903321.1		c.-189+78C>T		intron	N/A	ENSP00000573380.1
	CHGA	ENST00000216492.10	TSL:1 MANE Select	c.-270C>T		upstream_gene	N/A	ENSP00000216492.5	P10645
	CHGA	ENST00000334654.4	TSL:1	c.-270C>T		upstream_gene	N/A	ENSP00000334023.4	G5E968

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

African (AFR) AF: 0.183 AC: 721 AN: 3948

American (AMR) AF: 0.0988 AC: 388 AN: 3928

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 842 AN: 5144

East Asian (EAS) AF: 0.113 AC: 1466 AN: 12956

South Asian (SAS) AF: 0.207 AC: 291 AN: 1404

European-Finnish (FIN) AF: 0.237 AC: 3184 AN: 13426

Middle Eastern (MID) AF: 0.160 AC: 211 AN: 1316

European-Non Finnish (NFE) AF: 0.161 AC: 14902 AN: 92836

Other (OTH) AF: 0.164 AC: 1552 AN: 9478

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

African (AFR) AF: 0.181 AC: 7512 AN: 41568

American (AMR) AF: 0.109 AC: 1661 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.133 AC: 687 AN: 5164

South Asian (SAS) AF: 0.218 AC: 1054 AN: 4830

European-Finnish (FIN) AF: 0.243 AC: 2578 AN: 10610

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11384 AN: 67972

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.157 Hom.: 785

Bravo AF: 0.158

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		-0.060
PromoterAI		0.27	Neutral
Mutation Taster		=300/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9658638;

hg19: chr14-93389435;

COSMIC: COSV53664722;

COSMIC: COSV53664722;