rs2901964

chr1-15465931-C-Gchr1-15465931-C-T

Variant summary

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

The NM_033440.3(CELA2A):c.494-68C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,569,754 control chromosomes in the GnomAD database, including 45,287 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 0.32 (11165 hom., cov: 31)
  • Exomes 𝑓: 0.20 (34122 hom.)
• Consequence: CELA2A NM_033440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

CELA2A (HGNC:24609): (chymotrypsin like elastase 2A) 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 2A is secreted from the pancreas as a zymogen. In other species, elastase 2A has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, May 2009]

LOC105376767 (HGNC:):

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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELA2A	NM_033440.3	c.494-68C>G		intron_variant		ENST00000359621.5
LOC105376767	XR_002958256.2	n.367-1059G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELA2A	ENST00000359621.5	c.494-68C>G		intron_variant		1	NM_033440.3	P1
CELA2B	ENST00000494280.1	n.23C>G		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48950 AN: 151904 Hom.: 11136 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.205 AC: 290259 AN: 1417732 Hom.: 34122 Cov.: 25 AF XY: 0.204 AC XY: 144363 AN XY: 706034

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.0872

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.322 AC: 49027 AN: 152022 Hom.: 11165 Cov.: 31 AF XY: 0.317 AC XY: 23527 AN XY: 74306

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0768

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.310

Alfa AF: 0.193 Hom.: 1777

Bravo AF: 0.339

Asia WGS AF: 0.186 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.83
Dann	Benign	0.39

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: rs2901964; hg19: chr1-15792426; COSMIC: COSV62747293; COSMIC: COSV62747293;