Variant rs3748050 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000259938.7(CLPS):c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,563,648 control chromosomes in the GnomAD database, including 22,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 1725 hom., cov: 42)

Exomes 𝑓: 0.26 ( 20803 hom. )

Consequence

CLPS
ENST00000259938.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

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:

LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]

LHFPL5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CLPS	NM_001832.4 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/3	ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2 linkuse as main transcript	c.-143A>G	5_prime_UTR_variant	1/4		NP_001239526.1
CLPS	NM_001252598.2 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/2		NP_001239527.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CLPS	ENST00000259938.7 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/3	1	NM_001832.4	ENSP00000259938	P1
CLPS	ENST00000616014.3 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/2	1		ENSP00000483589
LHFPL5	ENST00000651132.1 linkuse as main transcript	c.-323+2T>C	splice_donor_variant				ENSP00000498322	P1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

37655

AN:

149142

Hom.:

1726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.0567

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.246

AC:

60747

AN:

247286

Hom.:

2935

AF XY:

0.246

AC XY:

32868

AN XY:

133704

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.256

AC:

362784

AN:

1414388

Hom.:

20803

Cov.:

AF XY:

0.256

AC XY:

180398

AN XY:

704644

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.245

Gnomad4 EAS exome

AF:

0.0414

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.252

AC:

37680

AN:

149260

Hom.:

1725

Cov.:

AF XY:

0.249

AC XY:

18172

AN XY:

72968

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.0560

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.268

Hom.:

310

Asia WGS

AF:

0.184

AC:

643

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.56

DANN

Benign

0.54

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