dbSNP rs742711: CHGB:p.Arg417His (chr20-5923394-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.1250G>A(p.Arg417His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,613,774 control chromosomes in the GnomAD database, including 61,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4809 hom., cov: 31)

Exomes 𝑓: 0.28 ( 57158 hom. )

Consequence

CHGB
NM_001819.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.77

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:

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 (MetaRNN=9.033978E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGB	NM_001819.3 link	c.1250G>A	p.Arg417His	missense_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.1250G>A	p.Arg417His	missense_variant	Exon 4 of 5	1	NM_001819.3	ENSP00000368244.4		P05060

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35368

AN:

151916

Hom.:

4803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.214

GnomAD2 exomes

AF:

0.279

AC:

70062

AN:

250998

AF XY:

0.276

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.275

AC:

402435

AN:

1461740

Hom.:

57158

Cov.:

AF XY:

0.275

AC XY:

199703

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.0979

AC:

3278

AN:

33480

American (AMR)

AF:

0.316

AC:

14130

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4754

AN:

26136

East Asian (EAS)

AF:

0.396

AC:

15716

AN:

39700

South Asian (SAS)

AF:

0.259

AC:

22303

AN:

86258

European-Finnish (FIN)

AF:

0.365

AC:

19439

AN:

53312

Middle Eastern (MID)

AF:

0.192

AC:

1105

AN:

5768

European-Non Finnish (NFE)

AF:

0.275

AC:

306313

AN:

1111972

Other (OTH)

AF:

0.255

AC:

15397

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

18542

37084

55625

74167

92709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10286

20572

30858

41144

51430

<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:

0.233

AC:

35402

AN:

152034

Hom.:

4809

Cov.:

AF XY:

0.236

AC XY:

17574

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.104

AC:

4308

AN:

41492

American (AMR)

AF:

0.245

AC:

3743

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

614

AN:

3472

East Asian (EAS)

AF:

0.379

AC:

1953

AN:

5156

South Asian (SAS)

AF:

0.263

AC:

1268

AN:

4816

European-Finnish (FIN)

AF:

0.362

AC:

3823

AN:

10548

Middle Eastern (MID)

AF:

0.134

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.279

AC:

18947

AN:

67962

Other (OTH)

AF:

0.220

AC:

464

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1289

2578

3867

5156

6445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.257

Hom.:

18077

Bravo

AF:

0.218

TwinsUK

AF:

0.289

AC:

1072

ALSPAC

AF:

0.269

AC:

1035

ESP6500AA

AF:

0.118

AC:

521

ESP6500EA

AF:

0.265

AC:

2277

ExAC

AF:

0.273

AC:

33128

Asia WGS

AF:

0.338

AC:

1178

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0080

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.43

MetaRNN

Benign

0.00090

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.27

PhyloP100

-2.8

PrimateAI

Benign

0.21

PROVEAN

Benign

0.64

REVEL

Benign

0.035

Sift

Benign

0.31

Sift4G

Benign

0.24

Polyphen

0.013

Vest4

0.035

MPC

0.11

ClinPred

0.015

GERP RS

-11

Varity_R

0.017

gMVP

0.19

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