Variant 20-5923000-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001819.3(CHGB):c.856G>A(p.Gly286Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,610,722 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

CHGB
NM_001819.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058779716).

BP6

Variant 20-5923000-G-A is Benign according to our data. Variant chr20-5923000-G-A is described in ClinVar as [Benign]. Clinvar id is 744891.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHGB	NM_001819.3 linkuse as main transcript	c.856G>A	p.Gly286Arg	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.856G>A	p.Gly286Arg	missense_variant	4/5	1	NM_001819.3	P1
CHGB	ENST00000455042.1 linkuse as main transcript	c.796G>A	p.Gly266Arg	missense_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00659

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000538

AC:

130

AN:

241436

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

130886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000892

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00715

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000927

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000208

AC:

303

AN:

1458566

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

725332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000681

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00717

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000210

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00621

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.000535

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.67

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.033

Sift

Benign

0.27

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.75

P;.

Vest4

0.29

MVP

0.37

MPC

0.50

ClinPred

0.058

GERP RS

3.1

Varity_R

0.081

gMVP

0.23

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