1-21980883-C-A

Variant names:

• chr1-21980883-C-A
• NM_007352.4:c.189C>A
• CELA3B p.Ile63Ile

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007352.4(CELA3B):​c.189C>A​(p.Ile63Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I63I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: CELA3B NM_007352.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-2.3 with no splicing effect.

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.189C>A	p.Ile63Ile	synonymous	Exon 3 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.189C>A	p.Ile63Ile	synonymous	Exon 3 of 8	ENSP00000338369.6	P08861
	CELA3B	ENST00000374666.1	TSL:3	n.240C>A		non_coding_transcript_exon	Exon 3 of 5
	CELA3B	ENST00000400277.2	TSL:5	c.-219C>A		upstream_gene	N/A	ENSP00000383135.2	A0A0A0MSA6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.25
DANN	Benign	0.75
PhyloP100		-2.3
PromoterAI		-0.050	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-22307376;