20-5922742-A-C

Position:

• chr20-5922742-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001819.3(CHGB):​c.598A>C​(p.Asn200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0632 in 1,613,572 control chromosomes in the GnomAD database, including 6,376 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1451 hom., cov: 32)
  • Exomes 𝑓: 0.059 (4925 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050234795).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGB	NM_001819.3	c.598A>C	p.Asn200His	missense_variant	4/5	ENST00000378961.9	NP_001810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9	c.598A>C	p.Asn200His	missense_variant	4/5	1	NM_001819.3	ENSP00000368244	P1
CHGB	ENST00000455042.1	c.538A>C	p.Asn180His	missense_variant	5/5	3		ENSP00000416643

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16450 AN: 152054 Hom.: 1446 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0967

GnomAD3 exomes AF: 0.104 AC: 26201 AN: 251228 Hom.: 2466 AF XY: 0.0982 AC XY: 13336 AN XY: 135850

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.0684

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.0195

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0783

GnomAD4 exome AF: 0.0585 AC: 85529 AN: 1461400 Hom.: 4925 Cov.: 64 AF XY: 0.0604 AC XY: 43920 AN XY: 727026

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.0647

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0205

Gnomad4 NFE exome AF: 0.0365

Gnomad4 OTH exome AF: 0.0738

GnomAD4 genome AF: 0.108 AC: 16486 AN: 152172 Hom.: 1451 Cov.: 32 AF XY: 0.111 AC XY: 8281 AN XY: 74400

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0168

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0605 Hom.: 1045

Bravo AF: 0.124

TwinsUK AF: 0.0334 AC: 124

ALSPAC AF: 0.0381 AC: 147

ESP6500AA AF: 0.204 AC: 899

ESP6500EA AF: 0.0374 AC: 322

ExAC AF: 0.102 AC: 12322

Asia WGS AF: 0.176 AC: 611 AN: 3478

EpiCase AF: 0.0419

EpiControl AF: 0.0421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.057
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.077	T;T
Polyphen		0.025	B;.
Vest4		0.054
MPC		0.12
ClinPred		0.0088	T
GERP RS		-1.7
Varity_R		0.16
gMVP		0.077

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

Other links and lift over

dbSNP: rs881118; hg19: chr20-5903388; COSMIC: COSV66760368; COSMIC: COSV66760368;