14-92923058-A-G

Variant names:

• chr14-92923058-A-G
• rs7159323
• XM_011536370.3:c.-189+46A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_011536370.3(CHGA):​c.-189+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CHGA XM_011536370.3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGA	XM_011536370.3	c.-189+46A>G		intron_variant	Intron 1 of 8		XP_011534672.1
CHGA	NM_001275.4	c.-302A>G		upstream_gene_variant		ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2	c.-302A>G		upstream_gene_variant			NP_001288619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10	c.-302A>G		upstream_gene_variant		1	NM_001275.4	ENSP00000216492.5
CHGA	ENST00000334654.4	c.-302A>G		upstream_gene_variant		1		ENSP00000334023.4
CHGA	ENST00000556076.5	n.-302A>G		upstream_gene_variant		5		ENSP00000450801.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 2

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		-0.15
PromoterAI		0.57	Over-expression

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;