1-15482272-G-C

Position:

• chr1-15482272-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015849.3(CELA2B):​c.235G>C​(p.Gly79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELA2B NM_015849.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04596731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELA2B	NM_015849.3	c.235G>C	p.Gly79Arg	missense_variant	4/8	ENST00000375910.8	NP_056933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELA2B	ENST00000375910.8	c.235G>C	p.Gly79Arg	missense_variant	4/8	1	NM_015849.3	ENSP00000365075.3
CELA2B	ENST00000422901.1	c.292G>C	p.Gly98Arg	missense_variant	4/4	5		ENSP00000399811.1
CELA2B	ENST00000494280.1	n.584G>C		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.012
DANN	Benign	0.21
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.12	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.28	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	4.2	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.96	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0	B;.
Vest4		0.051
MutPred		0.49		Gain of solvent accessibility (P = 0.0097);.;
MVP		0.18
MPC		0.36
ClinPred		0.048	T
GERP RS		-6.2
Varity_R		0.047
gMVP		0.55

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: rs3820071; hg19: chr1-15808767;