Genetic Variant NM_001819.3:c.199G>T (chr20-5922343-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001819.3(CHGB):c.199G>T(p.Asp67Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,540,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

CHGB
NM_001819.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10401958).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001819.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	NM_001819.3	MANE Select	c.199G>T	p.Asp67Tyr	missense	Exon 4 of 5	NP_001810.2	P05060

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHGB	ENST00000378961.9	TSL:1 MANE Select	c.199G>T	p.Asp67Tyr	missense	Exon 4 of 5	ENSP00000368244.4	P05060
CHGB	ENST00000966395.1		c.199G>T	p.Asp67Tyr	missense	Exon 4 of 5	ENSP00000636454.1
CHGB	ENST00000886261.1		c.199G>T	p.Asp67Tyr	missense	Exon 4 of 5	ENSP00000556320.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000121

AC:

AN:

205814

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000771

AC:

107

AN:

1387984

Hom.:

Cov.:

AF XY:

0.0000763

AC XY:

AN XY:

681846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30636

American (AMR)

AF:

0.0000606

AC:

AN:

33026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21956

East Asian (EAS)

AF:

0.00

AC:

AN:

38752

South Asian (SAS)

AF:

0.000106

AC:

AN:

75224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51318

Middle Eastern (MID)

AF:

0.000371

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.0000865

AC:

AN:

1074698

Other (OTH)

AF:

0.0000351

AC:

AN:

56978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000125

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000167

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

M_CAP

Benign

0.025

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

REVEL

Benign

0.079

Sift

Uncertain

0.012

Sift4G

Uncertain

0.018

Polyphen

0.20

Vest4

0.23

MVP

0.40

MPC

0.12

ClinPred

0.039

GERP RS

3.8

Varity_R

0.22

gMVP

0.18

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over