rs4815876

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-5922207-C-A
• chr20-5922207-C-G
• chr20-5922207-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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.

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>A		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>A		intron	N/A	ENSP00000368244.4
	CHGB	ENST00000455042.1	TSL:3	c.131-128C>A		intron	N/A	ENSP00000416643.1

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

African (AFR) AF: 0.350 AC: 8822 AN: 25224

American (AMR) AF: 0.545 AC: 8993 AN: 16500

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 4567 AN: 16656

East Asian (EAS) AF: 0.529 AC: 17571 AN: 33220

South Asian (SAS) AF: 0.441 AC: 17720 AN: 40136

European-Finnish (FIN) AF: 0.419 AC: 14879 AN: 35526

Middle Eastern (MID) AF: 0.345 AC: 1100 AN: 3186

European-Non Finnish (NFE) AF: 0.366 AC: 326270 AN: 890406

Other (OTH) AF: 0.375 AC: 17378 AN: 46340

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

African (AFR) AF: 0.364 AC: 15085 AN: 41450

American (AMR) AF: 0.476 AC: 7266 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 980 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2792 AN: 5158

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4816

European-Finnish (FIN) AF: 0.416 AC: 4391 AN: 10564

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25414 AN: 67974

Other (OTH) AF: 0.369 AC: 778 AN: 2110

Alfa AF: 0.380 Hom.: 3864

Bravo AF: 0.392

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.49
PhyloP100		-0.50
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: rs4815876; hg19: chr20-5902853; COSMIC: COSV66761965; COSMIC: COSV66761965;