1-21984233-G-C

Variant names:

• chr1-21984233-G-C
• rs767856879
• NM_007352.4:c.544G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007352.4(CELA3B):​c.544G>C​(p.Val182Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V182M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CELA3B NM_007352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 5 publications found

Genes affected

CELA3B (HGNC:15945): (chymotrypsin like elastase 3B) 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. Unlike other elastases, elastase 3B has little elastolytic activity. Like most of the human elastases, elastase 3B is secreted from the pancreas as a zymogen and, like other serine proteases such as trypsin, chymotrypsin and kallikrein, it has a digestive function in the intestine. Elastase 3B preferentially cleaves proteins after alanine residues. Elastase 3B may also function in the intestinal transport and metabolism of cholesterol. Both elastase 3A and elastase 3B have been referred to as protease E and as elastase 1, and excretion of this protein in fecal material is frequently used as a measure of pancreatic function in clinical assays. [provided by RefSeq, May 2009]

ENSG00000285959 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007352.4. 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
	CELA3B	NM_007352.4	MANE Select	c.544G>C	p.Val182Leu	missense	Exon 6 of 8	NP_031378.1	P08861

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA3B	ENST00000337107.11	TSL:1 MANE Select	c.544G>C	p.Val182Leu	missense	Exon 6 of 8	ENSP00000338369.6	P08861
	CELA3B	ENST00000400277.2	TSL:5	c.253G>C	p.Val85Leu	missense	Exon 3 of 5	ENSP00000383135.2	A0A0A0MSA6
	ENSG00000285959	ENST00000650360.1		n.270G>C		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	0.52	N
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.025	D
Sift4G	Benign	0.13	T
Polyphen		0.50	P
Vest4		0.33
MutPred		0.72		Loss of catalytic residue at V182 (P = 0.0436)
MVP		0.71
MPC		0.39
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.53
gMVP		0.60
Mutation Taster		=50/50

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: rs767856879; hg19: chr1-22310726;