14-92928234-T-A

Position:

• chr14-92928234-T-A

Variant summary

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

The ENST00000216492.10(CHGA):​c.256+616T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,082 control chromosomes in the GnomAD database, including 4,836 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 0.25 (4836 hom., cov: 33)
• Consequence: CHGA ENST00000216492.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	NM_001275.4	c.256+616T>A		intron_variant		ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2	c.256+616T>A		intron_variant			NP_001288619.1
CHGA	XM_011536370.3	c.256+616T>A		intron_variant			XP_011534672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10	c.256+616T>A		intron_variant		1	NM_001275.4	ENSP00000216492	P1
CHGA	ENST00000334654.4	c.256+616T>A		intron_variant		1		ENSP00000334023
CHGA	ENST00000556076.5	c.*45+616T>A		intron_variant, NMD_transcript_variant		5		ENSP00000450801
CHGA	ENST00000553866.1	n.206+616T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37710 AN: 151964 Hom.: 4838 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.248 AC: 37704 AN: 152082 Hom.: 4836 Cov.: 33 AF XY: 0.241 AC XY: 17957 AN XY: 74356

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.286

Alfa AF: 0.256 Hom.: 673

Bravo AF: 0.252

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs735726; hg19: chr14-93394579;