dbSNP rs7159323: CHGA:c.-189+46A>C (chr14-92923058-A-C) – 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+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 258,476 control chromosomes in the GnomAD database, including 83,081 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 0.81 ( 49990 hom., cov: 33)

Exomes 𝑓: 0.79 ( 33091 hom. )

Consequence

CHGA
XM_011536370.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

Publications

12 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:

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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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHGA	XM_011536370.3 link	c.-189+46A>C	intron_variant	Intron 1 of 8		XP_011534672.1
CHGA	NM_001275.4 link	c.-302A>C	upstream_gene_variant		ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2 link	c.-302A>C	upstream_gene_variant			NP_001288619.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
CHGA	ENST00000216492.10 link	c.-302A>C	upstream_gene_variant	1	NM_001275.4	ENSP00000216492.5
CHGA	ENST00000334654.4 link	c.-302A>C	upstream_gene_variant	1		ENSP00000334023.4
CHGA	ENST00000556076.5 link	n.-302A>C	upstream_gene_variant	5		ENSP00000450801.1

Frequencies

GnomAD3 genomes

AF:

0.808

AC:

122819

AN:

152084

Hom.:

49957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.675

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.948

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.807

GnomAD4 exome

AF:

0.787

AC:

83642

AN:

106274

Hom.:

33091

Cov.:

AF XY:

0.785

AC XY:

42685

AN XY:

54410

show subpopulations

African (AFR)

AF:

0.887

AC:

2732

AN:

3080

American (AMR)

AF:

0.807

AC:

2304

AN:

2856

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

2930

AN:

3904

East Asian (EAS)

AF:

0.955

AC:

8848

AN:

9264

South Asian (SAS)

AF:

0.827

AC:

848

AN:

1026

European-Finnish (FIN)

AF:

0.734

AC:

6760

AN:

9208

Middle Eastern (MID)

AF:

0.831

AC:

726

AN:

874

European-Non Finnish (NFE)

AF:

0.766

AC:

52839

AN:

68942

Other (OTH)

AF:

0.794

AC:

5655

AN:

7120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

833

1665

2498

3330

4163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

222

444

666

888

1110

<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:

0.808

AC:

122909

AN:

152202

Hom.:

49990

Cov.:

AF XY:

0.807

AC XY:

60030

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.889

AC:

36951

AN:

41558

American (AMR)

AF:

0.818

AC:

12510

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2588

AN:

3472

East Asian (EAS)

AF:

0.948

AC:

4914

AN:

5182

South Asian (SAS)

AF:

0.827

AC:

3996

AN:

4830

European-Finnish (FIN)

AF:

0.729

AC:

7724

AN:

10594

Middle Eastern (MID)

AF:

0.853

AC:

249

AN:

292

European-Non Finnish (NFE)

AF:

0.760

AC:

51651

AN:

67956

Other (OTH)

AF:

0.809

AC:

1710

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1228

2456

3685

4913

6141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.682

Hom.:

1907

Bravo

AF:

0.814

Asia WGS

AF:

0.893

AC:

3106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

-0.15

PromoterAI

0.097

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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