chr20-5922207-C-G

Variant names:

• chr20-5922207-C-G
• rs4815876
• NM_001819.3:c.191-128C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001819.3(CHGB):​c.191-128C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000009 in 1,110,578 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: CHGB NM_001819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.191-128C>G		intron	N/A	NP_001810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.191-128C>G		intron	N/A	ENSP00000368244.4
	CHGB	ENST00000455042.1	TSL:3	c.131-128C>G		intron	N/A	ENSP00000416643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.00e-7 AC: 1 AN: 1110578 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 536132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25286

American (AMR) AF: 0.00 AC: 0 AN: 16522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16686

East Asian (EAS) AF: 0.00 AC: 0 AN: 33258

South Asian (SAS) AF: 0.00 AC: 0 AN: 40242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 893334

Other (OTH) AF: 0.00 AC: 0 AN: 46466

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.62
PhyloP100		-0.50

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: rs4815876; hg19: chr20-5902853;