rs9658635

Positions:

• chr14-92922732-T-C

Variant summary

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

The XM_011536370.3(CHGA):​c.-469T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,074 control chromosomes in the GnomAD database, including 6,674 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 0.29 (6674 hom., cov: 33)
• Consequence: CHGA XM_011536370.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	XM_011536370.3	c.-469T>C		5_prime_UTR_variant	1/9		XP_011534672.1
		n.92922732T>C		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43692 AN: 151956 Hom.: 6666 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.288 AC: 43737 AN: 152074 Hom.: 6674 Cov.: 33 AF XY: 0.291 AC XY: 21608 AN XY: 74322

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.273

Alfa AF: 0.238 Hom.: 4606

Bravo AF: 0.279

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9658635; hg19: chr14-93389077;