Genetic Variant CLPS:c.84+412C>T (chr6-35796793-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001832.4(CLPS):c.84+412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 486 hom., cov: 45)

Exomes 𝑓: 0.15 ( 145 hom. )

Failed GnomAD Quality Control

Consequence

CLPS
NM_001832.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.968

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-35796793-G-A is Benign according to our data. Variant chr6-35796793-G-A is described in ClinVar as [Benign]. Clinvar id is 402546.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLPS	NM_001832.4 link	c.84+412C>T	intron_variant	Intron 1 of 2	ENST00000259938.7	NP_001823.1	P04118
CLPS	NM_001252597.2 link	c.42+16C>T	intron_variant	Intron 2 of 3		NP_001239526.1	A0A087WZW1
CLPS	NM_001252598.2 link	c.84+412C>T	intron_variant	Intron 1 of 1		NP_001239527.1	A0A087X0Q7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLPS	ENST00000259938.7 link	c.84+412C>T	intron_variant	Intron 1 of 2	1	NM_001832.4	ENSP00000259938.2	P04118
CLPS	ENST00000616014.3 link	c.84+412C>T	intron_variant	Intron 1 of 1	1		ENSP00000483589.1	A0A087X0Q7
CLPS	ENST00000622413.2 link	c.42+16C>T	intron_variant	Intron 1 of 2	5		ENSP00000482919.1	A0A087WZW1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

36841

AN:

146996

Hom.:

482

Cov.:

FAILED QC

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.142

AC:

15003

AN:

105302

Hom.:

AF XY:

0.138

AC XY:

7978

AN XY:

57726

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.150

AC:

38557

AN:

256718

Hom.:

145

Cov.:

AF XY:

0.145

AC XY:

21348

AN XY:

146842

show subpopulations

Gnomad4 AFR exome

AF:

0.336

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.251

AC:

36884

AN:

147110

Hom.:

486

Cov.:

AF XY:

0.247

AC XY:

17782

AN XY:

71888

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.180

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.216

Hom.:

Asia WGS

AF:

0.203

AC:

704

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.7

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over