dbSNP rs9658638: CHGA:c.-189+78C>T (chr14-92923090-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_011536370.3(CHGA):c.-189+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 296,680 control chromosomes in the GnomAD database, including 4,374 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 0.17 ( 2310 hom., cov: 33)

Exomes 𝑓: 0.16 ( 2064 hom. )

Consequence

CHGA
XM_011536370.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHGA	XM_011536370.3 link	c.-189+78C>T	intron_variant	Intron 1 of 8		XP_011534672.1	P10645
CHGA	NM_001275.4 link	c.-270C>T	upstream_gene_variant		ENST00000216492.10	NP_001266.1	P10645Q86T07
CHGA	NM_001301690.2 link	c.-270C>T	upstream_gene_variant			NP_001288619.1	P10645G5E968Q86T07

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CHGA	ENST00000216492.10 link	c.-270C>T	upstream_gene_variant	1	NM_001275.4	ENSP00000216492.5	P10645
CHGA	ENST00000334654.4 link	c.-270C>T	upstream_gene_variant	1		ENSP00000334023.4	G5E968
CHGA	ENST00000556076.5 link	n.-270C>T	upstream_gene_variant	5		ENSP00000450801.1	G3V2Q7

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25947

AN:

152126

Hom.:

2303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.163

AC:

23557

AN:

144436

Hom.:

2064

Cov.:

AF XY:

0.163

AC XY:

12018

AN XY:

73940

show subpopulations

African (AFR)

AF:

0.183

AC:

721

AN:

3948

American (AMR)

AF:

0.0988

AC:

388

AN:

3928

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

842

AN:

5144

East Asian (EAS)

AF:

0.113

AC:

1466

AN:

12956

South Asian (SAS)

AF:

0.207

AC:

291

AN:

1404

European-Finnish (FIN)

AF:

0.237

AC:

3184

AN:

13426

Middle Eastern (MID)

AF:

0.160

AC:

211

AN:

1316

European-Non Finnish (NFE)

AF:

0.161

AC:

14902

AN:

92836

Other (OTH)

AF:

0.164

AC:

1552

AN:

9478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

916

1832

2748

3664

4580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25975

AN:

152244

Hom.:

2310

Cov.:

AF XY:

0.174

AC XY:

12937

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.181

AC:

7512

AN:

41568

American (AMR)

AF:

0.109

AC:

1661

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

616

AN:

3472

East Asian (EAS)

AF:

0.133

AC:

687

AN:

5164

South Asian (SAS)

AF:

0.218

AC:

1054

AN:

4830

European-Finnish (FIN)

AF:

0.243

AC:

2578

AN:

10610

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11384

AN:

67972

Other (OTH)

AF:

0.158

AC:

333

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1117

2234

3350

4467

5584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

785

Bravo

AF:

0.158

Asia WGS

AF:

0.183

AC:

636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

-0.060

PromoterAI

0.27

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over