rs1278311003

Variant names:

• chr1-21981169-G-C
• rs1278311003
• NM_007352.4:c.359G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007352.4(CELA3B):​c.359G>C​(p.Cys120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CELA3B NM_007352.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16445562).

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.359G>C	p.Cys120Ser	missense	Exon 4 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.359G>C	p.Cys120Ser	missense	Exon 4 of 8	ENSP00000338369.6	P08861
	CELA3B	ENST00000400277.2	TSL:5	c.68G>C	p.Cys23Ser	missense	Exon 1 of 5	ENSP00000383135.2	A0A0A0MSA6
	CELA3B	ENST00000374666.1	TSL:3	n.410G>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459878 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726232

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4170

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 74134

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.54
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.82	N
PhyloP100		1.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.17
Sift	Benign	0.82	T
Sift4G	Benign	0.79	T
Polyphen		0.064	B
Vest4		0.50
MutPred		0.37		Loss of stability (P = 0.0371)
MVP		0.072
MPC		0.29
ClinPred		0.14	T
GERP RS		3.9
PromoterAI		-0.0090	Neutral
Varity_R		0.74
gMVP		0.77
Mutation Taster		=66/34	polymorphism

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: rs1278311003; hg19: chr1-22307662;