Genetic Variant NM_001025200.4:c.171C>G (chr16-75205978-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001025200.4(CTRB2):c.171C>G(p.Phe57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.0000086 ( 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: 2.50

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.171C>G	p.Phe57Leu	missense	Exon 3 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.171C>G	p.Phe57Leu	missense	Exon 3 of 7	ENSP00000303963.8	Q6GPI1
CTRB2	ENST00000567767.5	TSL:5	c.15C>G	p.Phe5Leu	missense	Exon 1 of 4	ENSP00000457279.1	H3BTQ4
CTRB2	ENST00000481611.1	TSL:2	n.1085C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000561

AC:

AN:

71292

AF XY:

0.0000555

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000856

AC:

AN:

817308

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

410902

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

18736

American (AMR)

AF:

0.000293

AC:

AN:

23914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16558

East Asian (EAS)

AF:

0.00

AC:

AN:

32756

South Asian (SAS)

AF:

0.00

AC:

AN:

54818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

594838

Other (OTH)

AF:

0.00

AC:

AN:

37976

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000515075), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.361

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.62

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.42

PhyloP100

2.5

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.60

Sift

Benign

0.066

Sift4G

Benign

0.16

Polyphen

0.025

Vest4

0.45

MutPred

0.54

Loss of methylation at K54 (P = 0.1013)

MVP

0.75

MPC

0.12

ClinPred

0.21

GERP RS

3.4

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.80

gMVP

0.69

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