20-5923382-C-T

Variant names:

• chr20-5923382-C-T
• rs742710
• NM_001819.3:c.1238C>T

Variant summary

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

The NM_001819.3(CHGB):​c.1238C>T​(p.Pro413Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,613,708 control chromosomes in the GnomAD database, including 7,003 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1744 hom., cov: 31)
  • Exomes 𝑓: 0.060 (5259 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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=0.0050937235).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGB	NM_001819.3	c.1238C>T	p.Pro413Leu	missense_variant	Exon 4 of 5	ENST00000378961.9	NP_001810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9	c.1238C>T	p.Pro413Leu	missense_variant	Exon 4 of 5	1	NM_001819.3	ENSP00000368244.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17823 AN: 151858 Hom.: 1736 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.107 AC: 26964 AN: 251012 Hom.: 2625 AF XY: 0.100 AC XY: 13629 AN XY: 135654

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.0703

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.0195

Gnomad NFE exome AF: 0.0376

Gnomad OTH exome AF: 0.0824

GnomAD4 exome AF: 0.0598 AC: 87460 AN: 1461732 Hom.: 5259 Cov.: 58 AF XY: 0.0616 AC XY: 44782 AN XY: 727152

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.0669

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0205

Gnomad4 NFE exome AF: 0.0369

Gnomad4 OTH exome AF: 0.0762

GnomAD4 genome AF: 0.118 AC: 17864 AN: 151976 Hom.: 1744 Cov.: 31 AF XY: 0.120 AC XY: 8949 AN XY: 74294

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0579 Hom.: 1252

Bravo AF: 0.135

TwinsUK AF: 0.0337 AC: 125

ALSPAC AF: 0.0389 AC: 150

ESP6500AA AF: 0.235 AC: 1034

ESP6500EA AF: 0.0387 AC: 333

ExAC AF: 0.105 AC: 12771

Asia WGS AF: 0.179 AC: 622 AN: 3478

EpiCase AF: 0.0423

EpiControl AF: 0.0427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.030
DANN	Benign	0.49
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.010
Sift	Benign	0.31	T
Sift4G	Benign	0.065	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.084
ClinPred		0.00074	T
GERP RS		-6.0
Varity_R		0.022
gMVP		0.14

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: rs742710; hg19: chr20-5904028; COSMIC: COSV66759777; COSMIC: COSV66759777;