Genetic Variant CHGA:c.*87T>C (chr14-92934971-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001275.4(CHGA):c.*87T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,175,492 control chromosomes in the GnomAD database, including 317,475 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 0.78 ( 46967 hom., cov: 32)

Exomes 𝑓: 0.72 ( 270508 hom. )

Consequence

CHGA
NM_001275.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.99

Publications

27 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHGA	NM_001275.4 link	c.*87T>C	3_prime_UTR_variant	Exon 8 of 8	ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2 link	c.*87T>C	3_prime_UTR_variant	Exon 7 of 7		NP_001288619.1
CHGA	XM_011536370.3 link	c.*87T>C	3_prime_UTR_variant	Exon 9 of 9		XP_011534672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10 link	c.*87T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001275.4	ENSP00000216492.5
CHGA	ENST00000334654.4 link	c.*87T>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000334023.4

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118592

AN:

151978

Hom.:

46928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.700

Gnomad EAS

AF:

0.946

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.783

GnomAD4 exome

AF:

0.724

AC:

741139

AN:

1023396

Hom.:

270508

Cov.:

AF XY:

0.727

AC XY:

370849

AN XY:

510108

show subpopulations

African (AFR)

AF:

0.904

AC:

18890

AN:

20894

American (AMR)

AF:

0.763

AC:

12916

AN:

16934

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

13705

AN:

19274

East Asian (EAS)

AF:

0.949

AC:

28477

AN:

30006

South Asian (SAS)

AF:

0.803

AC:

45913

AN:

57190

European-Finnish (FIN)

AF:

0.698

AC:

31681

AN:

45404

Middle Eastern (MID)

AF:

0.751

AC:

2609

AN:

3476

European-Non Finnish (NFE)

AF:

0.705

AC:

553643

AN:

785462

Other (OTH)

AF:

0.744

AC:

33305

AN:

44756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

9655

19310

28964

38619

48274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12982

25964

38946

51928

64910

<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:

0.780

AC:

118685

AN:

152096

Hom.:

46967

Cov.:

AF XY:

0.781

AC XY:

58065

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.900

AC:

37374

AN:

41534

American (AMR)

AF:

0.785

AC:

12008

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.700

AC:

2432

AN:

3472

East Asian (EAS)

AF:

0.946

AC:

4862

AN:

5142

South Asian (SAS)

AF:

0.820

AC:

3959

AN:

4828

European-Finnish (FIN)

AF:

0.701

AC:

7428

AN:

10600

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.709

AC:

48141

AN:

67912

Other (OTH)

AF:

0.785

AC:

1658

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1274

2549

3823

5098

6372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.845

Hom.:

11739

Bravo

AF:

0.789

Asia WGS

AF:

0.886

AC:

3082

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.027

(source)

DANN

Benign

0.24

PhyloP100

-4.0

Mutation Taster

=100/0

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