rs236146

Variant names:

• chr20-5916716-G-A
• rs236146
• NM_001819.3:c.97-110G>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.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
• Publications: 3 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]

ENSG00000310389 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.97-110G>A		intron	N/A	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.97-110G>A		intron	N/A	ENSP00000368244.4	P05060
	CHGB	ENST00000966395.1		c.97-110G>A		intron	N/A	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.97-110G>A		intron	N/A	ENSP00000556320.1

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

African (AFR) AF: 0.0908 AC: 1856 AN: 20436

American (AMR) AF: 0.232 AC: 9795 AN: 42310

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 3472 AN: 20578

East Asian (EAS) AF: 0.401 AC: 14628 AN: 36450

South Asian (SAS) AF: 0.259 AC: 18048 AN: 69722

European-Finnish (FIN) AF: 0.315 AC: 16376 AN: 51966

Middle Eastern (MID) AF: 0.196 AC: 874 AN: 4458

European-Non Finnish (NFE) AF: 0.251 AC: 124412 AN: 495412

Other (OTH) AF: 0.232 AC: 8782 AN: 37920

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

African (AFR) AF: 0.0922 AC: 3828 AN: 41506

American (AMR) AF: 0.202 AC: 3087 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3472

East Asian (EAS) AF: 0.385 AC: 1990 AN: 5172

South Asian (SAS) AF: 0.268 AC: 1295 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3339 AN: 10572

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17404 AN: 67966

Other (OTH) AF: 0.206 AC: 435 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		0.15
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: rs236146; hg19: chr20-5897362;