rs735726

Variant names:

• chr14-92928234-T-A
• rs735726
• NM_001275.4:c.256+616T>A

Variant summary

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

The NM_001275.4(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 NM_001275.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 1 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=-0.95).
• 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 rank	MANE	Protein	UniProt
CHGA	NM_001275.4	c.256+616T>A		intron_variant	Intron 4 of 7	ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2	c.256+616T>A		intron_variant	Intron 4 of 6		NP_001288619.1
CHGA	XM_011536370.3	c.256+616T>A		intron_variant	Intron 5 of 8		XP_011534672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10	c.256+616T>A		intron_variant	Intron 4 of 7	1	NM_001275.4	ENSP00000216492.5
CHGA	ENST00000334654.4	c.256+616T>A		intron_variant	Intron 4 of 6	1		ENSP00000334023.4
CHGA	ENST00000553866.1	n.206+616T>A		intron_variant	Intron 3 of 5	3
CHGA	ENST00000556076.5	n.*45+616T>A		intron_variant	Intron 3 of 4	5		ENSP00000450801.1

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

African (AFR) AF: 0.244 AC: 10133 AN: 41478

American (AMR) AF: 0.231 AC: 3525 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3472

East Asian (EAS) AF: 0.110 AC: 568 AN: 5172

South Asian (SAS) AF: 0.188 AC: 907 AN: 4814

European-Finnish (FIN) AF: 0.184 AC: 1951 AN: 10578

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18633 AN: 67974

Other (OTH) AF: 0.286 AC: 603 AN: 2110

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs735726; hg19: chr14-93394579;