20-5911261-A-T

Variant names:

• chr20-5911261-A-T
• rs236141
• NM_001819.3:c.-373A>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.-373A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,998 control chromosomes in the GnomAD database, including 16,690 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 0.46 (16690 hom., cov: 33)
• Consequence: CHGB NM_001819.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 9 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 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.-373A>T		upstream_gene	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.-373A>T		upstream_gene	N/A	ENSP00000368244.4	P05060
	CHGB	ENST00000966395.1		c.-373A>T		upstream_gene	N/A	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.-373A>T		upstream_gene	N/A	ENSP00000556320.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69655 AN: 151878 Hom.: 16653 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.459 AC: 69750 AN: 151998 Hom.: 16690 Cov.: 33 AF XY: 0.465 AC XY: 34544 AN XY: 74302

African (AFR) AF: 0.486 AC: 20145 AN: 41484

American (AMR) AF: 0.507 AC: 7739 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3464

East Asian (EAS) AF: 0.890 AC: 4606 AN: 5178

South Asian (SAS) AF: 0.520 AC: 2503 AN: 4814

European-Finnish (FIN) AF: 0.446 AC: 4714 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27277 AN: 67922

Other (OTH) AF: 0.441 AC: 928 AN: 2104

Alfa AF: 0.423 Hom.: 1682

Bravo AF: 0.462

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.50
PhyloP100		-0.55
PromoterAI		-0.078	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs236141; hg19: chr20-5891907;