rs10927792

chr1-15483381-G-Achr1-15483381-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015849.3(CELA2B):c.474G>A(p.Thr158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,613,732 control chromosomes in the GnomAD database, including 60,859 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 0.29 (6812 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54047 hom.)
• Consequence: CELA2B NM_015849.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.05

Genes affected

CELA2B (HGNC:29995): (chymotrypsin like elastase 2B) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2B is secreted from the pancreas as a zymogen. In other species, elastase 2B has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-6.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELA2B	NM_015849.3	c.474G>A	p.Thr158=	synonymous_variant	5/8	ENST00000375910.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELA2B	ENST00000375910.8	c.474G>A	p.Thr158=	synonymous_variant	5/8	1	NM_015849.3	P1
CELA2B	ENST00000494280.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43800 AN: 151998 Hom.: 6802 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.250

GnomAD3 exomes AF: 0.286 AC: 71799 AN: 250742 Hom.: 11561 AF XY: 0.275 AC XY: 37219 AN XY: 135514

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.561

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.264 AC: 385415 AN: 1461616 Hom.: 54047 Cov.: 39 AF XY: 0.260 AC XY: 189191 AN XY: 727112

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.288 AC: 43842 AN: 152116 Hom.: 6812 Cov.: 32 AF XY: 0.290 AC XY: 21541 AN XY: 74360

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.251

Alfa AF: 0.255 Hom.: 2168

Bravo AF: 0.294

Asia WGS AF: 0.386 AC: 1343 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.0090
Dann	Benign	0.85

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: rs10927792; hg19: chr1-15809876;