rs910122

chr20-5922677-G-Achr20-5922677-G-T

Variant summary

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

The NM_001819.3(CHGB):c.533G>A(p.Arg178Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,613,706 control chromosomes in the GnomAD database, including 122,503 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.38 (11403 hom., cov: 32)
  • Exomes 𝑓: 0.38 (111100 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=1.5072046E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHGB	NM_001819.3	c.533G>A	p.Arg178Gln	missense_variant	4/5	ENST00000378961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHGB	ENST00000378961.9	c.533G>A	p.Arg178Gln	missense_variant	4/5	1	NM_001819.3	P1
CHGB	ENST00000455042.1	c.473G>A	p.Arg158Gln	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57746 AN: 151856 Hom.: 11386 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.425 AC: 106604 AN: 250832 Hom.: 24295 AF XY: 0.417 AC XY: 56521 AN XY: 135626

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.557

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.385 AC: 562604 AN: 1461732 Hom.: 111100 Cov.: 67 AF XY: 0.386 AC XY: 280430 AN XY: 727128

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.380 AC: 57816 AN: 151974 Hom.: 11403 Cov.: 32 AF XY: 0.386 AC XY: 28676 AN XY: 74248

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.365

Alfa AF: 0.375 Hom.: 27257

Bravo AF: 0.381

TwinsUK AF: 0.377 AC: 1397

ALSPAC AF: 0.367 AC: 1414

ESP6500AA AF: 0.335 AC: 1478

ESP6500EA AF: 0.358 AC: 3075

ExAC AF: 0.416 AC: 50568

Asia WGS AF: 0.523 AC: 1819 AN: 3478

EpiCase AF: 0.363

EpiControl AF: 0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.0030
Dann	Benign	0.58
DEOGEN2	Benign	0.056	T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.48	T;T
MetaRNN	Benign	0.000015	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.024
Sift	Benign	0.49	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	B;.
Vest4		0.021
MPC		0.096
ClinPred		0.021	T
GERP RS		-11
Varity_R		0.023
gMVP		0.076

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: rs910122; hg19: chr20-5903323; COSMIC: COSV100972995; COSMIC: COSV100972995;