Variant rs9658668 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001275.4(CHGA):c.1163C>T(p.Pro388Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,610,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

CHGA
NM_001275.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.191

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:

CHGA (HGNC:):

CHGA links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005293399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	NM_001275.4 linkuse as main transcript	c.1163C>T	p.Pro388Leu	missense_variant	7/8	ENST00000216492.10	NP_001266.1	P10645Q86T07
CHGA	NM_001301690.2 linkuse as main transcript	c.710C>T	p.Pro237Leu	missense_variant	6/7		NP_001288619.1	P10645G5E968Q86T07
CHGA	XM_011536370.3 linkuse as main transcript	c.1163C>T	p.Pro388Leu	missense_variant	8/9		XP_011534672.1	P10645

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHGA	ENST00000216492.10 linkuse as main transcript	c.1163C>T	p.Pro388Leu	missense_variant	7/8	1	NM_001275.4	ENSP00000216492.5	P10645
CHGA	ENST00000334654.4 linkuse as main transcript	c.710C>T	p.Pro237Leu	missense_variant	6/7	1		ENSP00000334023.4	G5E968
CHGA	ENST00000556876.1 linkuse as main transcript	n.381C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000386

AC:

AN:

238524

Hom.:

AF XY:

0.000398

AC XY:

AN XY:

130492

show subpopulations

Gnomad AFR exome

AF:

0.00423

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000672

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000848

Gnomad OTH exome

AF:

0.000520

GnomAD4 exome

AF:

0.000214

AC:

312

AN:

1458666

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

725432

show subpopulations

Gnomad4 AFR exome

AF:

0.00439

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.000631

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152240

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00412

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.00120

ESP6500AA

AF:

0.00320

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000380

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.3

DANN

Benign

0.91

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.051

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.020

N;.

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.040

Sift

Benign

0.25

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0050

B;B

Vest4

0.092

MVP

0.34

MPC

0.20

ClinPred

0.0085

GERP RS

0.27

Varity_R

0.048

gMVP

0.065

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