Variant 20-5922495-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001819.3(CHGB):c.351G>C(p.Lys117Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,310 control chromosomes in the GnomAD database, including 1,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.062 ( 971 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 831 hom. )

Consequence

CHGB
NM_001819.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.596

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005486071).

BP6

Variant 20-5922495-G-C is Benign according to our data. Variant chr20-5922495-G-C is described in ClinVar as [Benign]. Clinvar id is 3037531.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHGB	NM_001819.3 linkuse as main transcript	c.351G>C	p.Lys117Asn	missense_variant	4/5	ENST00000378961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHGB	ENST00000378961.9 linkuse as main transcript	c.351G>C	p.Lys117Asn	missense_variant	4/5	1	NM_001819.3	P1
CHGB	ENST00000455042.1 linkuse as main transcript	c.291G>C	p.Lys97Asn	missense_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9399

AN:

152078

Hom.:

968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0166

AC:

4147

AN:

249540

Hom.:

382

AF XY:

0.0127

AC XY:

1718

AN XY:

134950

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.00299

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.000492

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00704

AC:

10281

AN:

1461114

Hom.:

831

Cov.:

AF XY:

0.00627

AC XY:

4557

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0618

AC:

9412

AN:

152196

Hom.:

971

Cov.:

AF XY:

0.0588

AC XY:

4378

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.0256

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.0701

ESP6500AA

AF:

0.209

AC:

922

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.0197

AC:

2389

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHGB-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

Cadd

Benign

4.8

Dann

Benign

0.92

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.027

Sift

Benign

0.23

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.17

B;.

Vest4

0.032

MutPred

0.41

Loss of ubiquitination at K117 (P = 0.0017);.;

MPC

0.16

ClinPred

0.0012

GERP RS

1.4

Varity_R

0.12

gMVP

0.058

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over