rs3766160

Positions:

• chr1-15482377-G-A

Variant summary

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

The NM_015849.3(CELA2B):​c.340G>A​(p.Asp114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,674 control chromosomes in the GnomAD database, including 57,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5616 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51863 hom.)
• Consequence: CELA2B NM_015849.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.4650486E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELA2B	NM_015849.3	c.340G>A	p.Asp114Asn	missense_variant	4/8	ENST00000375910.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELA2B	ENST00000375910.8	c.340G>A	p.Asp114Asn	missense_variant	4/8	1	NM_015849.3	P1
CELA2B	ENST00000494280.1	n.689G>A		non_coding_transcript_exon_variant	5/6	5
CELA2B	ENST00000422901.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39938 AN: 151940 Hom.: 5612 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.274 AC: 68796 AN: 251436 Hom.: 10478 AF XY: 0.265 AC XY: 36004 AN XY: 135890

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.547

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.259 AC: 378902 AN: 1461616 Hom.: 51863 Cov.: 33 AF XY: 0.256 AC XY: 186371 AN XY: 727120

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.263 AC: 39955 AN: 152058 Hom.: 5616 Cov.: 32 AF XY: 0.264 AC XY: 19597 AN XY: 74292

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.230

Alfa AF: 0.253 Hom.: 12663

Bravo AF: 0.265

TwinsUK AF: 0.262 AC: 970

ALSPAC AF: 0.250 AC: 965

ESP6500AA AF: 0.261 AC: 1151

ESP6500EA AF: 0.245 AC: 2111

ExAC AF: 0.271 AC: 32906

Asia WGS AF: 0.361 AC: 1256 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.2
DANN	Benign	0.37
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00098	N
LIST_S2	Benign	0.042	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.056
MPC		0.30
ClinPred		0.000016	T
GERP RS		0.47
Varity_R		0.037
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3766160; hg19: chr1-15808872;