rs236146

Positions:

• chr20-5916716-G-A

Variant summary

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

The NM_001819.3(CHGB):​c.97-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 931,366 control chromosomes in the GnomAD database, including 30,590 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 0.21 (4023 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26567 hom.)
• Consequence: CHGB NM_001819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

CHGB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGB	NM_001819.3	c.97-110G>A		intron_variant		ENST00000378961.9	NP_001810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9	c.97-110G>A		intron_variant		1	NM_001819.3	ENSP00000368244.4
CHGB	ENST00000455042.1	c.37-110G>A		intron_variant		3		ENSP00000416643.1
CHGB	ENST00000488832.1	n.876-110G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32187 AN: 151996 Hom.: 4016 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.254 AC: 198243 AN: 779252 Hom.: 26567 AF XY: 0.255 AC XY: 104678 AN XY: 411230

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.212 AC: 32219 AN: 152114 Hom.: 4023 Cov.: 32 AF XY: 0.216 AC XY: 16049 AN XY: 74390

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.206

Alfa AF: 0.240 Hom.: 621

Bravo AF: 0.196

Asia WGS AF: 0.334 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.63

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: rs236146; hg19: chr20-5897362;