14-92923058-A-C

Position:

• chr14-92923058-A-C

Variant summary

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

The XM_011536370.3(CHGA):​c.-189+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 258,476 control chromosomes in the GnomAD database, including 83,081 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 0.81 (49990 hom., cov: 33)
  • Exomes 𝑓: 0.79 (33091 hom.)
• Consequence: CHGA XM_011536370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	XM_011536370.3	c.-189+46A>C		intron_variant			XP_011534672.1
		n.92923058A>C		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122819 AN: 152084 Hom.: 49957 Cov.: 33

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.787 AC: 83642 AN: 106274 Hom.: 33091 Cov.: 2 AF XY: 0.785 AC XY: 42685 AN XY: 54410

Gnomad4 AFR exome AF: 0.887

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.827

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.808 AC: 122909 AN: 152202 Hom.: 49990 Cov.: 33 AF XY: 0.807 AC XY: 60030 AN XY: 74406

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.809

Alfa AF: 0.682 Hom.: 1907

Bravo AF: 0.814

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7159323; hg19: chr14-93389403;