chr1-15485937-A-G

Variant names:

• chr1-15485937-A-G
• rs6429745
• NM_015849.3:c.530A>G

Variant summary

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

The NM_015849.3(CELA2B):​c.530A>G​(p.Gln177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,614,190 control chromosomes in the GnomAD database, including 805,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.99 (75337 hom., cov: 32)
  • Exomes 𝑓: 1.0 (730031 hom.)
• Consequence: CELA2B NM_015849.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 (MetaRNN=6.408965E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2B	NM_015849.3	c.530A>G	p.Gln177Arg	missense_variant	Exon 6 of 8	ENST00000375910.8	NP_056933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2B	ENST00000375910.8	c.530A>G	p.Gln177Arg	missense_variant	Exon 6 of 8	1	NM_015849.3	ENSP00000365075.3
CELA2B	ENST00000488764.1	n.77A>G		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151364 AN: 152188 Hom.: 75277 Cov.: 32

Gnomad AFR AF: 0.982

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.994

GnomAD2 exomes AF: 0.998 AC: 251051 AN: 251466 AF XY: 0.999

Gnomad AFR exome AF: 0.980

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1460964 AN: 1461884 Hom.: 730031 Cov.: 63 AF XY: 0.999 AC XY: 726843 AN XY: 727246

African (AFR) AF: 0.981 AC: 32843 AN: 33480

American (AMR) AF: 0.998 AC: 44640 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26136 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39691 AN: 39698

South Asian (SAS) AF: 1.00 AC: 86236 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.998 AC: 5755 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111934 AN: 1112006

Other (OTH) AF: 0.999 AC: 60309 AN: 60396

GnomAD4 genome AF: 0.995 AC: 151483 AN: 152306 Hom.: 75337 Cov.: 32 AF XY: 0.995 AC XY: 74096 AN XY: 74484

African (AFR) AF: 0.982 AC: 40828 AN: 41562

American (AMR) AF: 0.996 AC: 15232 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10611 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68026 AN: 68032

Other (OTH) AF: 0.994 AC: 2104 AN: 2116

Alfa AF: 0.999 Hom.: 105077

Bravo AF: 0.994

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.979 AC: 4315

ESP6500EA AF: 1.00 AC: 8598

ExAC AF: 0.998 AC: 121192

Asia WGS AF: 0.999 AC: 3475 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.0
DANN	Benign	0.88
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.034	T
MetaRNN	Benign	6.4e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.17
Sift	Benign	0.38	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.33
ClinPred		0.0027	T
GERP RS		-2.8
Varity_R		0.081
gMVP		0.46
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

Publications

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Other links and lift over

dbSNP: rs6429745; hg19: chr1-15812432; COSMIC: COSV107489857; COSMIC: COSV107489857;