Variant rs9658655 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001275.4(CHGA):c.792G>C(p.Glu264Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,577,272 control chromosomes in the GnomAD database, including 10,297 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1498 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8799 hom. )

Consequence

CHGA
NM_001275.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.804

Variant links:

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]

CHGA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003715247).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGA	NM_001275.4 link	c.792G>C	p.Glu264Asp	missense_variant	Exon 6 of 8	ENST00000216492.10	NP_001266.1	P10645Q86T07
CHGA	XM_011536370.3 link	c.792G>C	p.Glu264Asp	missense_variant	Exon 7 of 9		XP_011534672.1	P10645
CHGA	NM_001301690.2 link	c.356-684G>C		intron_variant	Intron 5 of 6		NP_001288619.1	P10645G5E968Q86T07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10 link	c.792G>C	p.Glu264Asp	missense_variant	Exon 6 of 8	1	NM_001275.4	ENSP00000216492.5		P10645

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19220

AN:

152062

Hom.:

1497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0793

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0808

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.131

AC:

29566

AN:

225826

Hom.:

2467

AF XY:

0.128

AC XY:

15464

AN XY:

121086

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.0491

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.0801

Gnomad NFE exome

AF:

0.0809

Gnomad OTH exome

AF:

0.0991

GnomAD4 exome

AF:

0.101

AC:

143541

AN:

1425092

Hom.:

8799

Cov.:

AF XY:

0.102

AC XY:

71615

AN XY:

703606

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.0492

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0836

Gnomad4 NFE exome

AF:

0.0845

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.126

AC:

19250

AN:

152180

Hom.:

1498

Cov.:

AF XY:

0.127

AC XY:

9428

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.0793

Gnomad4 NFE

AF:

0.0807

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0952

Hom.:

180

Bravo

AF:

0.135

TwinsUK

AF:

0.0920

AC:

341

ALSPAC

AF:

0.0906

AC:

349

ESP6500AA

AF:

0.180

AC:

791

ESP6500EA

AF:

0.0836

AC:

719

ExAC

AF:

0.125

AC:

15165

Asia WGS

AF:

0.202

AC:

704

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.46

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

REVEL

Benign

0.097

Sift

Benign

0.089

Sift4G

Benign

0.23

Polyphen

0.87

Vest4

0.035

MutPred

0.099

Gain of MoRF binding (P = 0.1125);

MPC

0.25

ClinPred

0.024

GERP RS

4.0

Varity_R

0.086

gMVP

0.076

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over