Genetic Variant NM_001025200.4:c.586G>A (chr16-75204817-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001025200.4(CTRB2):c.586G>A(p.Asp196Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTRB2
NM_001025200.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.478

Publications

0 publications found

Variant links:

Genes affected

CTRB2 (HGNC:2522): (chymotrypsinogen B2) This gene encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This CTRB2 gene is located head-to-head with the related CTRB1 gene. Some human populations have an alternate haplotype which inverts a 16.6 Kb region containing portions of intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2 genes. In this inversion haplotype exon 1 and flanking sequence is swapped in CTRB1 and CTRB2. This inversion is associated with differential gene expression and increased risk for chronic pancreatitis. The GRCh38 assembly represents the minor allele for SNP rs8048956 of the CTRB1 gene. SNP rs8048956 is diagnostic for this inversion. [provided by RefSeq, Jan 2021]

CTRB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21511868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025200.4. 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
	CTRB2	NM_001025200.4	MANE Select	c.586G>A	p.Asp196Asn	missense	Exon 6 of 7	NP_001020371.3	Q6GPI1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTRB2	ENST00000303037.13	TSL:1 MANE Select	c.586G>A	p.Asp196Asn	missense	Exon 6 of 7	ENSP00000303963.8	Q6GPI1
CTRB2	ENST00000562106.5	TSL:3	c.325G>A	p.Asp109Asn	missense	Exon 3 of 4	ENSP00000454599.1	H3BMY1
CTRB2	ENST00000562387.1	TSL:3	c.334G>A	p.Asp112Asn	missense	Exon 3 of 4	ENSP00000455207.1	H3BP92

Frequencies

GnomAD3 genomes

AF:

0.0000148

AC:

AN:

134918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000153

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000731

AC:

AN:

136888

AF XY:

0.0000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000315

AC:

AN:

1269810

Hom.:

Cov.:

AF XY:

0.00000639

AC XY:

AN XY:

626256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29902

American (AMR)

AF:

0.00

AC:

AN:

33586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23126

East Asian (EAS)

AF:

0.0000286

AC:

AN:

34974

South Asian (SAS)

AF:

0.00

AC:

AN:

75356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3852

European-Non Finnish (NFE)

AF:

0.00000206

AC:

AN:

968972

Other (OTH)

AF:

0.0000188

AC:

AN:

53206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000148

AC:

AN:

134918

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37428

American (AMR)

AF:

0.000153

AC:

AN:

13088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3236

East Asian (EAS)

AF:

0.00

AC:

AN:

4564

South Asian (SAS)

AF:

0.00

AC:

AN:

4022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60850

Other (OTH)

AF:

0.00

AC:

AN:

1774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000301

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.054

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.89

PhyloP100

0.48

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.19

Sift

Benign

0.18

Sift4G

Benign

0.30

Polyphen

0.0070

Vest4

0.15

MutPred

0.61

Gain of MoRF binding (P = 0.0394)

MVP

0.78

MPC

0.096

ClinPred

0.088

GERP RS

1.0

Varity_R

0.27

gMVP

0.62

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over