Variant 14-92932756-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000216492.10(CHGA):c.1195C>T(p.Arg399Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,605,442 control chromosomes in the GnomAD database, including 18,533 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R399Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1486 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17047 hom. )

Consequence

CHGA
ENST00000216492.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.883

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031467676).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 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.1195C>T	p.Arg399Trp	missense_variant	7/8	ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2 linkuse as main transcript	c.742C>T	p.Arg248Trp	missense_variant	6/7		NP_001288619.1
CHGA	XM_011536370.3 linkuse as main transcript	c.1195C>T	p.Arg399Trp	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.1195C>T	p.Arg399Trp	missense_variant	7/8	1	NM_001275.4	ENSP00000216492	P1
CHGA	ENST00000334654.4 linkuse as main transcript	c.742C>T	p.Arg248Trp	missense_variant	6/7	1		ENSP00000334023
CHGA	ENST00000556876.1 linkuse as main transcript	n.413C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18714

AN:

152038

Hom.:

1483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.0870

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.154

AC:

35476

AN:

229818

Hom.:

3132

AF XY:

0.151

AC XY:

18970

AN XY:

125506

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.0840

Gnomad EAS exome

AF:

0.205

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.149

AC:

216612

AN:

1453284

Hom.:

17047

Cov.:

AF XY:

0.147

AC XY:

106220

AN XY:

722078

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.0856

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.123

AC:

18720

AN:

152158

Hom.:

1486

Cov.:

AF XY:

0.125

AC XY:

9335

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.0870

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.142

Hom.:

1500

Bravo

AF:

0.126

TwinsUK

AF:

0.141

AC:

524

ALSPAC

AF:

0.155

AC:

598

ESP6500AA

AF:

0.0340

AC:

148

ESP6500EA

AF:

0.141

AC:

1200

ExAC

AF:

0.138

AC:

16625

Asia WGS

AF:

0.141

AC:

490

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.19

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.029

Sift

Uncertain

0.027

D;T

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.063

MPC

0.54

ClinPred

0.045

GERP RS

1.2

Varity_R

0.16

gMVP

0.13

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