Genetic Variant CHGB:p.Glu368Glu (chr20-5923248-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001819.3(CHGB):c.1104A>G(p.Glu368Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,492 control chromosomes in the GnomAD database, including 135,307 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 0.47 ( 17602 hom., cov: 31)

Exomes 𝑓: 0.39 ( 117705 hom. )

Consequence

CHGB
NM_001819.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.639

Publications

26 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.639 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGB	NM_001819.3 link	c.1104A>G	p.Glu368Glu	synonymous_variant	Exon 4 of 5	ENST00000378961.9	NP_001810.2	P05060

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9 link	c.1104A>G	p.Glu368Glu	synonymous_variant	Exon 4 of 5	1	NM_001819.3	ENSP00000368244.4		P05060
CHGB	ENST00000455042.1 link	c.*175A>G		downstream_gene_variant		3		ENSP00000416643.1		A0A0A0MT66

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70739

AN:

151758

Hom.:

17568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.426

GnomAD2 exomes

AF:

0.448

AC:

112549

AN:

250954

AF XY:

0.435

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.558

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.395

AC:

576723

AN:

1461614

Hom.:

117705

Cov.:

AF XY:

0.394

AC XY:

286640

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.627

AC:

20997

AN:

33478

American (AMR)

AF:

0.620

AC:

27715

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7434

AN:

26134

East Asian (EAS)

AF:

0.533

AC:

21154

AN:

39698

South Asian (SAS)

AF:

0.439

AC:

37828

AN:

86258

European-Finnish (FIN)

AF:

0.418

AC:

22259

AN:

53216

Middle Eastern (MID)

AF:

0.367

AC:

2119

AN:

5768

European-Non Finnish (NFE)

AF:

0.372

AC:

413198

AN:

1111944

Other (OTH)

AF:

0.398

AC:

24019

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

21182

42364

63547

84729

105911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13324

26648

39972

53296

66620

<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:

0.466

AC:

70831

AN:

151878

Hom.:

17602

Cov.:

AF XY:

0.469

AC XY:

34807

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.626

AC:

25920

AN:

41416

American (AMR)

AF:

0.507

AC:

7738

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

986

AN:

3466

East Asian (EAS)

AF:

0.542

AC:

2785

AN:

5136

South Asian (SAS)

AF:

0.454

AC:

2184

AN:

4806

European-Finnish (FIN)

AF:

0.414

AC:

4374

AN:

10556

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.375

AC:

25503

AN:

67932

Other (OTH)

AF:

0.430

AC:

909

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1822

3645

5467

7290

9112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.403

Hom.:

52099

Bravo

AF:

0.479

Asia WGS

AF:

0.544

AC:

1892

AN:

3478

EpiCase

AF:

0.366

EpiControl

AF:

0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.58

(source)

DANN

Benign

0.55

PhyloP100

-0.64

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