1-15483381-G-A

Variant names:

• chr1-15483381-G-A
• rs10927792
• NM_015849.3:c.474G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015849.3(CELA2B):​c.474G>A​(p.Thr158Thr) 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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015849.3. 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
	CELA2B	NM_015849.3	MANE Select	c.474G>A	p.Thr158Thr	synonymous	Exon 5 of 8	NP_056933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA2B	ENST00000375910.8	TSL:1 MANE Select	c.474G>A	p.Thr158Thr	synonymous	Exon 5 of 8	ENSP00000365075.3
	CELA2B	ENST00000494280.1	TSL:5	n.*13G>A		downstream_gene	N/A

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

GnomAD2 exomes AF: 0.286 AC: 71799 AN: 250742 AF XY: 0.275

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 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

African (AFR) AF: 0.321 AC: 10762 AN: 33478

American (AMR) AF: 0.361 AC: 16159 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4151 AN: 26116

East Asian (EAS) AF: 0.553 AC: 21966 AN: 39696

South Asian (SAS) AF: 0.196 AC: 16916 AN: 86230

European-Finnish (FIN) AF: 0.281 AC: 15000 AN: 53402

Middle Eastern (MID) AF: 0.151 AC: 872 AN: 5766

European-Non Finnish (NFE) AF: 0.255 AC: 283586 AN: 1111842

Other (OTH) AF: 0.265 AC: 16003 AN: 60378

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

African (AFR) AF: 0.325 AC: 13474 AN: 41482

American (AMR) AF: 0.328 AC: 5025 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2890 AN: 5156

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4824

European-Finnish (FIN) AF: 0.281 AC: 2981 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17161 AN: 67976

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.255 Hom.: 2200

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0090
DANN	Benign	0.85
PhyloP100		-6.0
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: rs10927792; hg19: chr1-15809876; COSMIC: COSV107489747; COSMIC: COSV107489747;