rs236152

Positions:

• chr20-5923202-C-G

Variant summary

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

The NM_001819.3(CHGB):​c.1058C>G​(p.Ala353Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,684 control chromosomes in the GnomAD database, including 135,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.47 (17600 hom., cov: 31)
  • Exomes 𝑓: 0.39 (117742 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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=1.9415429E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGB	NM_001819.3	c.1058C>G	p.Ala353Gly	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.1058C>G	p.Ala353Gly	missense_variant	4/5	1	NM_001819.3	ENSP00000368244.4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70749 AN: 151736 Hom.: 17566 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.449 AC: 112629 AN: 251100 Hom.: 27221 AF XY: 0.435 AC XY: 59024 AN XY: 135828

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.635

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.558

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.395 AC: 576852 AN: 1461828 Hom.: 117742 Cov.: 60 AF XY: 0.394 AC XY: 286703 AN XY: 727218

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.467 AC: 70841 AN: 151856 Hom.: 17600 Cov.: 31 AF XY: 0.469 AC XY: 34821 AN XY: 74204

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.433

Alfa AF: 0.389 Hom.: 9111

Bravo AF: 0.479

TwinsUK AF: 0.377 AC: 1398

ALSPAC AF: 0.367 AC: 1413

ESP6500AA AF: 0.621 AC: 2735

ESP6500EA AF: 0.359 AC: 3091

ExAC AF: 0.445 AC: 53995

Asia WGS AF: 0.544 AC: 1893 AN: 3476

EpiCase AF: 0.366

EpiControl AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.33
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.000019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.021
Sift	Benign	0.50	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.057
MPC		0.15
ClinPred		0.0039	T
GERP RS		-1.1
Varity_R		0.026
gMVP		0.19

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: rs236152; hg19: chr20-5903848; COSMIC: COSV66760634; COSMIC: COSV66760634;