chr20-5922742-A-C

Variant names:

• chr20-5922742-A-C
• rs881118
• NM_001819.3:c.598A>C

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 0.11 (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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

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.598A>C	p.Asn200His	missense	Exon 4 of 5	NP_001810.2	P05060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.598A>C	p.Asn200His	missense	Exon 4 of 5	ENSP00000368244.4	P05060
	CHGB	ENST00000966395.1		c.598A>C	p.Asn200His	missense	Exon 4 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.598A>C	p.Asn200His	missense	Exon 4 of 5	ENSP00000556320.1

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

GnomAD2 exomes AF: 0.104 AC: 26201 AN: 251228 AF XY: 0.0982

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 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

African (AFR) AF: 0.214 AC: 7154 AN: 33474

American (AMR) AF: 0.248 AC: 11107 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0647 AC: 1690 AN: 26134

East Asian (EAS) AF: 0.137 AC: 5441 AN: 39698

South Asian (SAS) AF: 0.157 AC: 13499 AN: 86248

European-Finnish (FIN) AF: 0.0205 AC: 1095 AN: 53414

Middle Eastern (MID) AF: 0.0834 AC: 481 AN: 5768

European-Non Finnish (NFE) AF: 0.0365 AC: 40604 AN: 1111570

Other (OTH) AF: 0.0738 AC: 4458 AN: 60378

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

African (AFR) AF: 0.213 AC: 8849 AN: 41482

American (AMR) AF: 0.181 AC: 2767 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.161 AC: 831 AN: 5172

South Asian (SAS) AF: 0.171 AC: 824 AN: 4818

European-Finnish (FIN) AF: 0.0168 AC: 178 AN: 10620

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2517 AN: 68000

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0626 Hom.: 2191

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 v4.9

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
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.73
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.057
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.077	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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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