NM_015849.3:c.639+124G>T

Variant names:

• chr1-15486170-G-T
• rs2861484
• NM_015849.3:c.639+124G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015849.3(CELA2B):​c.639+124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,256,708 control chromosomes in the GnomAD database, including 25,138 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 0.20 (3122 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22016 hom.)
• Consequence: CELA2B NM_015849.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 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.639+124G>T		intron	N/A	NP_056933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA2B	ENST00000375910.8	TSL:1 MANE Select	c.639+124G>T		intron	N/A	ENSP00000365075.3
	CELA2B	ENST00000488764.1	TSL:2	n.186+124G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29879 AN: 151980 Hom.: 3106 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.195 AC: 215441 AN: 1104610 Hom.: 22016 AF XY: 0.196 AC XY: 107963 AN XY: 551264

African (AFR) AF: 0.202 AC: 5163 AN: 25568

American (AMR) AF: 0.117 AC: 3710 AN: 31784

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 4739 AN: 18760

East Asian (EAS) AF: 0.0671 AC: 2501 AN: 37248

South Asian (SAS) AF: 0.204 AC: 13324 AN: 65358

European-Finnish (FIN) AF: 0.216 AC: 8600 AN: 39732

Middle Eastern (MID) AF: 0.246 AC: 1061 AN: 4312

European-Non Finnish (NFE) AF: 0.200 AC: 166956 AN: 834184

Other (OTH) AF: 0.197 AC: 9387 AN: 47664

GnomAD4 genome AF: 0.197 AC: 29920 AN: 152098 Hom.: 3122 Cov.: 32 AF XY: 0.195 AC XY: 14463 AN XY: 74350

African (AFR) AF: 0.207 AC: 8583 AN: 41514

American (AMR) AF: 0.152 AC: 2316 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3464

East Asian (EAS) AF: 0.0560 AC: 290 AN: 5178

South Asian (SAS) AF: 0.176 AC: 847 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2338 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14050 AN: 67966

Other (OTH) AF: 0.206 AC: 433 AN: 2100

Alfa AF: 0.203 Hom.: 2713

Bravo AF: 0.191

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.67
PhyloP100		-0.073
Mutation Taster		=99/1	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: rs2861484; hg19: chr1-15812665;