Variant rs9658667 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.1144G>A(p.Gly382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,611,068 control chromosomes in the GnomAD database, including 1,096 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1031 hom. )

Consequence

CHGA
NM_001275.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

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=0.0028131306).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHGA	NM_001275.4 linkuse as main transcript	c.1144G>A	p.Gly382Ser	missense_variant	7/8	ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2 linkuse as main transcript	c.691G>A	p.Gly231Ser	missense_variant	6/7		NP_001288619.1
CHGA	XM_011536370.3 linkuse as main transcript	c.1144G>A	p.Gly382Ser	missense_variant	8/9		XP_011534672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CHGA	ENST00000216492.10 linkuse as main transcript	c.1144G>A	p.Gly382Ser	missense_variant	7/8	1	NM_001275.4	ENSP00000216492	P1
CHGA	ENST00000334654.4 linkuse as main transcript	c.691G>A	p.Gly231Ser	missense_variant	6/7	1		ENSP00000334023
CHGA	ENST00000556876.1 linkuse as main transcript	n.362G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3633

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.0537

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0314

AC:

7517

AN:

239082

Hom.:

173

AF XY:

0.0336

AC XY:

4401

AN XY:

130806

show subpopulations

Gnomad AFR exome

AF:

0.00639

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0316

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.0613

Gnomad FIN exome

AF:

0.0161

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0343

AC:

50058

AN:

1458832

Hom.:

1031

Cov.:

AF XY:

0.0352

AC XY:

25555

AN XY:

725528

show subpopulations

Gnomad4 AFR exome

AF:

0.00493

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.0621

Gnomad4 SAS exome

AF:

0.0606

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0345

GnomAD4 genome

AF:

0.0238

AC:

3628

AN:

152236

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1751

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.0536

Gnomad4 SAS

AF:

0.0624

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0327

Hom.:

105

Bravo

AF:

0.0232

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0330

AC:

127

ESP6500AA

AF:

0.00594

AC:

ESP6500EA

AF:

0.0286

AC:

245

ExAC

AF:

0.0308

AC:

3729

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.18

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.095

Sift

Benign

0.050

D;T

Sift4G

Benign

0.28

T;T

Polyphen

0.53

P;D

Vest4

0.048

MPC

0.29

ClinPred

0.022

GERP RS

4.8

Varity_R

0.073

gMVP

0.11

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