rs10485493

Positions:

• chr20-5924604-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001819.3(CHGB):​c.1957-368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 152,208 control chromosomes in the GnomAD database, including 891 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 0.066 (891 hom., cov: 32)
• Consequence: CHGB NM_001819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGB	NM_001819.3	c.1957-368C>T		intron_variant		ENST00000378961.9	NP_001810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9	c.1957-368C>T		intron_variant		1	NM_001819.3	ENSP00000368244	P1

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10038 AN: 152090 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00609

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0662 AC: 10074 AN: 152208 Hom.: 891 Cov.: 32 AF XY: 0.0659 AC XY: 4903 AN XY: 74424

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0701

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00607

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0369 Hom.: 149

Bravo AF: 0.0796

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs10485493; hg19: chr20-5905250;