rs4815876

chr20-5922207-C-Achr20-5922207-C-T

Variant summary

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

The NM_001819.3(CHGB):c.191-128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,259,208 control chromosomes in the GnomAD database, including 92,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11908 hom., cov: 32)
  • Exomes 𝑓: 0.38 (80311 hom.)
• Consequence: CHGB NM_001819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHGB	NM_001819.3	c.191-128C>A		intron_variant		ENST00000378961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHGB	ENST00000378961.9	c.191-128C>A		intron_variant		1	NM_001819.3	P1
CHGB	ENST00000455042.1	c.131-128C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59254 AN: 151894 Hom.: 11889 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.377 AC: 417300 AN: 1107194 Hom.: 80311 AF XY: 0.378 AC XY: 202238 AN XY: 534522

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.390 AC: 59325 AN: 152014 Hom.: 11908 Cov.: 32 AF XY: 0.396 AC XY: 29436 AN XY: 74324

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.369

Alfa AF: 0.378 Hom.: 2194

Bravo AF: 0.392

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.1
Dann	Benign	0.49

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: rs4815876; hg19: chr20-5902853; COSMIC: COSV66761965; COSMIC: COSV66761965;