chr20-5925133-C-A

Variant names:

• chr20-5925133-C-A
• rs2821
• NM_001819.3:c.*84C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001819.3(CHGB):​c.*84C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 847,386 control chromosomes in the GnomAD database, including 57,537 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 0.35 (9328 hom., cov: 32)
  • Exomes 𝑓: 0.37 (48209 hom.)
• Consequence: CHGB NM_001819.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 21 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 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.*84C>A		3_prime_UTR	Exon 5 of 5	NP_001810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.*84C>A		3_prime_UTR	Exon 5 of 5	ENSP00000368244.4
	CHGB	ENST00000966395.1		c.*84C>A		3_prime_UTR	Exon 5 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.*84C>A		3_prime_UTR	Exon 5 of 5	ENSP00000556320.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52559 AN: 151908 Hom.: 9323 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.367 AC: 255437 AN: 695360 Hom.: 48209 Cov.: 9 AF XY: 0.366 AC XY: 133750 AN XY: 365616

African (AFR) AF: 0.273 AC: 4645 AN: 17018

American (AMR) AF: 0.219 AC: 5953 AN: 27128

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 8025 AN: 18316

East Asian (EAS) AF: 0.467 AC: 15763 AN: 33756

South Asian (SAS) AF: 0.326 AC: 19264 AN: 59086

European-Finnish (FIN) AF: 0.408 AC: 18942 AN: 46396

Middle Eastern (MID) AF: 0.428 AC: 1781 AN: 4158

European-Non Finnish (NFE) AF: 0.370 AC: 168213 AN: 454974

Other (OTH) AF: 0.372 AC: 12851 AN: 34528

GnomAD4 genome AF: 0.346 AC: 52578 AN: 152026 Hom.: 9328 Cov.: 32 AF XY: 0.348 AC XY: 25873 AN XY: 74302

African (AFR) AF: 0.279 AC: 11570 AN: 41468

American (AMR) AF: 0.304 AC: 4640 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1507 AN: 3472

East Asian (EAS) AF: 0.454 AC: 2348 AN: 5168

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4810

European-Finnish (FIN) AF: 0.428 AC: 4511 AN: 10540

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25215 AN: 67968

Other (OTH) AF: 0.374 AC: 790 AN: 2114

Alfa AF: 0.362 Hom.: 20629

Bravo AF: 0.338

Asia WGS AF: 0.359 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		2.7
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: rs2821; hg19: chr20-5905779;