chr20-5922677-G-A

Variant names:

• chr20-5922677-G-A
• rs910122
• NM_001819.3:c.533G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.38 (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
• Publications: 32 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=1.5072046E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 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.533G>A	p.Arg178Gln	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.533G>A	p.Arg178Gln	missense	Exon 4 of 5	ENSP00000368244.4	P05060
	CHGB	ENST00000966395.1		c.533G>A	p.Arg178Gln	missense	Exon 4 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.533G>A	p.Arg178Gln	missense	Exon 4 of 5	ENSP00000556320.1

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

GnomAD2 exomes AF: 0.425 AC: 106604 AN: 250832 AF XY: 0.417

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 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

African (AFR) AF: 0.323 AC: 10803 AN: 33480

American (AMR) AF: 0.601 AC: 26854 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7291 AN: 26136

East Asian (EAS) AF: 0.533 AC: 21146 AN: 39698

South Asian (SAS) AF: 0.438 AC: 37744 AN: 86252

European-Finnish (FIN) AF: 0.418 AC: 22334 AN: 53392

Middle Eastern (MID) AF: 0.347 AC: 2000 AN: 5768

European-Non Finnish (NFE) AF: 0.370 AC: 411751 AN: 1111896

Other (OTH) AF: 0.376 AC: 22681 AN: 60392

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

African (AFR) AF: 0.331 AC: 13702 AN: 41452

American (AMR) AF: 0.473 AC: 7225 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 980 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2780 AN: 5140

South Asian (SAS) AF: 0.454 AC: 2182 AN: 4810

European-Finnish (FIN) AF: 0.414 AC: 4378 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25374 AN: 67950

Other (OTH) AF: 0.365 AC: 766 AN: 2100

Alfa AF: 0.375 Hom.: 36462

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 v4.9

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
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.9
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.024
Sift	Benign	0.49	T
Sift4G	Benign	0.34	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
Mutation Taster		=99/1	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: rs910122; hg19: chr20-5903323; COSMIC: COSV100972995; COSMIC: COSV100972995;