Variant rs41270082 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001832.4(CLPS):c.325C>T(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,608,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0069 ( 0 hom., cov: 40)

Exomes 𝑓: 0.0094 ( 0 hom. )

Consequence

CLPS
NM_001832.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

CLPS (HGNC:2085): (colipase) The protein encoded by this gene is a cofactor needed by pancreatic lipase for efficient dietary lipid hydrolysis. It binds to the C-terminal, non-catalytic domain of lipase, thereby stabilizing an active conformation and considerably increasing the overall hydrophobic binding site. The gene product allows lipase to anchor noncovalently to the surface of lipid micelles, counteracting the destabilizing influence of intestinal bile salts. This cofactor is only expressed in pancreatic acinar cells, suggesting regulation of expression by tissue-specific elements. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

CLPS links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006454587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLPS	NM_001832.4 linkuse as main transcript	c.325C>T	p.Arg109Cys	missense_variant	3/3	ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2 linkuse as main transcript	c.283C>T	p.Arg95Cys	missense_variant	4/4		NP_001239526.1
CLPS	NM_001252598.2 linkuse as main transcript	c.202C>T	p.Arg68Cys	missense_variant	2/2		NP_001239527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CLPS	ENST00000259938.7 linkuse as main transcript	c.325C>T	p.Arg109Cys	missense_variant	3/3	1	NM_001832.4	ENSP00000259938	P1
CLPS	ENST00000616014.3 linkuse as main transcript	c.202C>T	p.Arg68Cys	missense_variant	2/2	1		ENSP00000483589
CLPS	ENST00000622413.2 linkuse as main transcript	c.283C>T	p.Arg95Cys	missense_variant	3/3	5		ENSP00000482919

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1046

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00851

AC:

2132

AN:

250422

Hom.:

AF XY:

0.00874

AC XY:

1183

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00737

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00802

GnomAD4 exome

AF:

0.00935

AC:

13623

AN:

1456370

Hom.:

Cov.:

AF XY:

0.00940

AC XY:

6808

AN XY:

724452

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00819

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00709

GnomAD4 genome

AF:

0.00689

AC:

1047

AN:

152062

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

526

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00998

Hom.:

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.0115

AC:

1398

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00989

EpiControl

AF:

0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;D;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

.;D;.

REVEL

Benign

0.027

Sift

Uncertain

0.0030

.;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.0010

.;B;.

Vest4

0.13

MPC

1.1

ClinPred

0.042

GERP RS

-0.61

Varity_R

0.12

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over