ENST00000903321.1:c.-189+46A>C

Variant names:

• chr14-92923058-A-C
• rs7159323
• ENST00000903321.1:c.-189+46A>C

Variant summary

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

The ENST00000903321.1(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 ENST00000903321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 12 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 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.-302A>C		upstream_gene	N/A	NP_001266.1	P10645
	CHGA	NM_001301690.2		c.-302A>C		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+46A>C		intron	N/A	ENSP00000573380.1
	CHGA	ENST00000216492.10	TSL:1 MANE Select	c.-302A>C		upstream_gene	N/A	ENSP00000216492.5	P10645
	CHGA	ENST00000334654.4	TSL:1	c.-302A>C		upstream_gene	N/A	ENSP00000334023.4	G5E968

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

African (AFR) AF: 0.887 AC: 2732 AN: 3080

American (AMR) AF: 0.807 AC: 2304 AN: 2856

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2930 AN: 3904

East Asian (EAS) AF: 0.955 AC: 8848 AN: 9264

South Asian (SAS) AF: 0.827 AC: 848 AN: 1026

European-Finnish (FIN) AF: 0.734 AC: 6760 AN: 9208

Middle Eastern (MID) AF: 0.831 AC: 726 AN: 874

European-Non Finnish (NFE) AF: 0.766 AC: 52839 AN: 68942

Other (OTH) AF: 0.794 AC: 5655 AN: 7120

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

African (AFR) AF: 0.889 AC: 36951 AN: 41558

American (AMR) AF: 0.818 AC: 12510 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2588 AN: 3472

East Asian (EAS) AF: 0.948 AC: 4914 AN: 5182

South Asian (SAS) AF: 0.827 AC: 3996 AN: 4830

European-Finnish (FIN) AF: 0.729 AC: 7724 AN: 10594

Middle Eastern (MID) AF: 0.853 AC: 249 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51651 AN: 67956

Other (OTH) AF: 0.809 AC: 1710 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		-0.15
PromoterAI		0.097	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7159323; hg19: chr14-93389403;