chr1-15484129-T-C

Variant names:

• chr1-15484129-T-C
• rs12130370
• NM_015849.3:c.493+729T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015849.3(CELA2B):​c.493+729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,882 control chromosomes in the GnomAD database, including 22,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22491 hom., cov: 31)
• Consequence: CELA2B NM_015849.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• Publications: 7 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2B	NM_015849.3	c.493+729T>C		intron_variant	Intron 5 of 7	ENST00000375910.8	NP_056933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2B	ENST00000375910.8	c.493+729T>C		intron_variant	Intron 5 of 7	1	NM_015849.3	ENSP00000365075.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80768 AN: 151766 Hom.: 22444 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80874 AN: 151882 Hom.: 22491 Cov.: 31 AF XY: 0.530 AC XY: 39360 AN XY: 74212

African (AFR) AF: 0.698 AC: 28900 AN: 41418

American (AMR) AF: 0.503 AC: 7675 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1330 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3131 AN: 5140

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5264 AN: 10530

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31205 AN: 67938

Other (OTH) AF: 0.501 AC: 1054 AN: 2104

Alfa AF: 0.482 Hom.: 65472

Bravo AF: 0.541

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs12130370; hg19: chr1-15810624;