14-92922685-A-G

Variant names:

• chr14-92922685-A-G
• rs9658634
• ENST00000903321.1:c.-516A>G

Variant summary

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

The ENST00000903321.1(CHGA):​c.-516A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,220 control chromosomes in the GnomAD database, including 45,722 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 0.77 (45722 hom., cov: 33)
• Consequence: CHGA ENST00000903321.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGA	ENST00000903321.1		c.-516A>G		5_prime_UTR	Exon 1 of 9	ENSP00000573380.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117636 AN: 152102 Hom.: 45694 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 117715 AN: 152220 Hom.: 45722 Cov.: 33 AF XY: 0.774 AC XY: 57611 AN XY: 74408

African (AFR) AF: 0.774 AC: 32133 AN: 41540

American (AMR) AF: 0.801 AC: 12252 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2566 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4917 AN: 5182

South Asian (SAS) AF: 0.828 AC: 3993 AN: 4824

European-Finnish (FIN) AF: 0.729 AC: 7713 AN: 10578

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51622 AN: 68008

Other (OTH) AF: 0.782 AC: 1654 AN: 2114

Alfa AF: 0.765 Hom.: 153003

Bravo AF: 0.774

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.53
PhyloP100		-1.2
PromoterAI		0.00010	Neutral

Splicing

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: rs9658634;

hg19: chr14-93389030;