rs742711

Variant names:

• chr20-5923394-G-A
• rs742711
• NM_001819.3:c.1250G>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.1250G>A​(p.Arg417His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,613,774 control chromosomes in the GnomAD database, including 61,967 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 0.23 (4809 hom., cov: 31)
  • Exomes 𝑓: 0.28 (57158 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 26 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=9.033978E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	NM_001819.3	MANE Select	c.1250G>A	p.Arg417His	missense	Exon 4 of 5	NP_001810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.1250G>A	p.Arg417His	missense	Exon 4 of 5	ENSP00000368244.4
	CHGB	ENST00000966395.1		c.1250G>A	p.Arg417His	missense	Exon 4 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.1250G>A	p.Arg417His	missense	Exon 4 of 5	ENSP00000556320.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35368 AN: 151916 Hom.: 4803 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.279 AC: 70062 AN: 250998 AF XY: 0.276

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.387

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.275 AC: 402435 AN: 1461740 Hom.: 57158 Cov.: 42 AF XY: 0.275 AC XY: 199703 AN XY: 727172

African (AFR) AF: 0.0979 AC: 3278 AN: 33480

American (AMR) AF: 0.316 AC: 14130 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4754 AN: 26136

East Asian (EAS) AF: 0.396 AC: 15716 AN: 39700

South Asian (SAS) AF: 0.259 AC: 22303 AN: 86258

European-Finnish (FIN) AF: 0.365 AC: 19439 AN: 53312

Middle Eastern (MID) AF: 0.192 AC: 1105 AN: 5768

European-Non Finnish (NFE) AF: 0.275 AC: 306313 AN: 1111972

Other (OTH) AF: 0.255 AC: 15397 AN: 60394

GnomAD4 genome AF: 0.233 AC: 35402 AN: 152034 Hom.: 4809 Cov.: 31 AF XY: 0.236 AC XY: 17574 AN XY: 74314

African (AFR) AF: 0.104 AC: 4308 AN: 41492

American (AMR) AF: 0.245 AC: 3743 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1953 AN: 5156

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4816

European-Finnish (FIN) AF: 0.362 AC: 3823 AN: 10548

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 290

European-Non Finnish (NFE) AF: 0.279 AC: 18947 AN: 67962

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.257 Hom.: 18077

Bravo AF: 0.218

TwinsUK AF: 0.289 AC: 1072

ALSPAC AF: 0.269 AC: 1035

ESP6500AA AF: 0.118 AC: 521

ESP6500EA AF: 0.265 AC: 2277

ExAC AF: 0.273 AC: 33128

Asia WGS AF: 0.338 AC: 1178 AN: 3478

EpiCase AF: 0.258

EpiControl AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0080
DANN	Benign	0.84
DEOGEN2	Benign	0.036	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.00090	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-2.8
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.035
Sift	Benign	0.31	T
Sift4G	Benign	0.24	T
Polyphen		0.013	B
Vest4		0.035
MPC		0.11
ClinPred		0.015	T
GERP RS		-11
Varity_R		0.017
gMVP		0.19
Mutation Taster		=100/0	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: rs742711; hg19: chr20-5904040; COSMIC: COSV66759649; COSMIC: COSV66759649;