Genetic Variant CHGB:c.97-110G>A (chr20-5916716-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001819.3(CHGB):c.97-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 931,366 control chromosomes in the GnomAD database, including 30,590 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 0.21 ( 4023 hom., cov: 32)

Exomes 𝑓: 0.25 ( 26567 hom. )

Consequence

CHGB
NM_001819.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

3 publications found

Variant links:

Genes affected

CHGB (HGNC:1930): (chromogranin B) This gene encodes a tyrosine-sulfated secretory protein abundant in peptidergic endocrine cells and neurons. This protein may serve as a precursor for regulatory peptides. [provided by RefSeq, Jan 2009]

CHGB links:

ENSG00000310389 (HGNC:):

ENSG00000310389 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGB	NM_001819.3 link	c.97-110G>A		intron_variant	Intron 2 of 4	ENST00000378961.9	NP_001810.2	P05060

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHGB	ENST00000378961.9 link	c.97-110G>A	intron_variant	Intron 2 of 4	1	NM_001819.3	ENSP00000368244.4	P05060
CHGB	ENST00000455042.1 link	c.37-110G>A	intron_variant	Intron 3 of 4	3		ENSP00000416643.1	A0A0A0MT66
CHGB	ENST00000488832.1 link	n.876-110G>A	intron_variant	Intron 1 of 1	2
ENSG00000310389	ENST00000849520.1 link	n.147+766C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32187

AN:

151996

Hom.:

4016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0923

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.254

AC:

198243

AN:

779252

Hom.:

26567

AF XY:

0.255

AC XY:

104678

AN XY:

411230

show subpopulations

African (AFR)

AF:

0.0908

AC:

1856

AN:

20436

American (AMR)

AF:

0.232

AC:

9795

AN:

42310

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

3472

AN:

20578

East Asian (EAS)

AF:

0.401

AC:

14628

AN:

36450

South Asian (SAS)

AF:

0.259

AC:

18048

AN:

69722

European-Finnish (FIN)

AF:

0.315

AC:

16376

AN:

51966

Middle Eastern (MID)

AF:

0.196

AC:

874

AN:

4458

European-Non Finnish (NFE)

AF:

0.251

AC:

124412

AN:

495412

Other (OTH)

AF:

0.232

AC:

8782

AN:

37920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7724

15448

23173

30897

38621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2426

4852

7278

9704

12130

<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:

0.212

AC:

32219

AN:

152114

Hom.:

4023

Cov.:

AF XY:

0.216

AC XY:

16049

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0922

AC:

3828

AN:

41506

American (AMR)

AF:

0.202

AC:

3087

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3472

East Asian (EAS)

AF:

0.385

AC:

1990

AN:

5172

South Asian (SAS)

AF:

0.268

AC:

1295

AN:

4824

European-Finnish (FIN)

AF:

0.316

AC:

3339

AN:

10572

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17404

AN:

67966

Other (OTH)

AF:

0.206

AC:

435

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1261

2522

3784

5045

6306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.240

Hom.:

621

Bravo

AF:

0.196

Asia WGS

AF:

0.334

AC:

1164

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

(source)

DANN

Benign

0.63

PhyloP100

0.15

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