rs3766160

Variant names:

• chr1-15482377-G-A
• rs3766160
• NM_015849.3:c.340G>A

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 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 (MetaRNN=2.4650486E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA2B	NM_015849.3	MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 4 of 8	NP_056933.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA2B	ENST00000375910.8	TSL:1 MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 4 of 8	ENSP00000365075.3
	CELA2B	ENST00000494280.1	TSL:5	n.689G>A		non_coding_transcript_exon	Exon 5 of 6
	CELA2B	ENST00000422901.1	TSL:5	c.*20G>A		downstream_gene	N/A	ENSP00000399811.1

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

GnomAD2 exomes AF: 0.274 AC: 68796 AN: 251436 AF XY: 0.265

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 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

African (AFR) AF: 0.255 AC: 8544 AN: 33476

American (AMR) AF: 0.317 AC: 14168 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4119 AN: 26132

East Asian (EAS) AF: 0.534 AC: 21199 AN: 39690

South Asian (SAS) AF: 0.195 AC: 16836 AN: 86244

European-Finnish (FIN) AF: 0.274 AC: 14650 AN: 53380

Middle Eastern (MID) AF: 0.150 AC: 864 AN: 5766

European-Non Finnish (NFE) AF: 0.255 AC: 283035 AN: 1111828

Other (OTH) AF: 0.256 AC: 15487 AN: 60384

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

African (AFR) AF: 0.256 AC: 10603 AN: 41498

American (AMR) AF: 0.284 AC: 4343 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2792 AN: 5152

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4816

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10552

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

European-Non Finnish (NFE) AF: 0.251 AC: 17092 AN: 67970

Other (OTH) AF: 0.230 AC: 486 AN: 2116

Alfa AF: 0.257 Hom.: 23343

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 v4.9

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
PhyloP100		0.10
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3766160; hg19: chr1-15808872; COSMIC: COSV107489861; COSMIC: COSV107489861;