chr14-92922685-A-G

Position:

• chr14-92922685-A-G

Variant summary

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

The XM_011536370.3(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 XM_011536370.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	XM_011536370.3	c.-516A>G		5_prime_UTR_variant	1/9		XP_011534672.1
		n.92922685A>G		intergenic_region

Ensembl

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

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

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.782

Alfa AF: 0.763 Hom.: 54216

Bravo AF: 0.774

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9658634; hg19: chr14-93389030;