Variant chr6-35797166-T-C 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.84+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,519,962 control chromosomes in the GnomAD database, including 21,230 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 0.21 ( 1374 hom., cov: 42)

Exomes 𝑓: 0.25 ( 19856 hom. )

Consequence

CLPS
ENST00000259938.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CLPS	NM_001832.4 linkuse as main transcript	c.84+39A>G	intron_variant	ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2 linkuse as main transcript	c.-57+39A>G	intron_variant		NP_001239526.1
CLPS	NM_001252598.2 linkuse as main transcript	c.84+39A>G	intron_variant		NP_001239527.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CLPS	ENST00000259938.7 linkuse as main transcript	c.84+39A>G	intron_variant	1	NM_001832.4	ENSP00000259938	P1
CLPS	ENST00000616014.3 linkuse as main transcript	c.84+39A>G	intron_variant	1		ENSP00000483589
LHFPL5	ENST00000651132.1 linkuse as main transcript		upstream_gene_variant			ENSP00000498322	P1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32051

AN:

149312

Hom.:

1374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.0674

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.228

AC:

55647

AN:

243668

Hom.:

2670

AF XY:

0.231

AC XY:

30387

AN XY:

131768

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.0598

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.249

AC:

340840

AN:

1370526

Hom.:

19856

Cov.:

AF XY:

0.248

AC XY:

169894

AN XY:

684420

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.0554

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.215

AC:

32062

AN:

149436

Hom.:

1374

Cov.:

AF XY:

0.212

AC XY:

15522

AN XY:

73048

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.0666

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.259

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.173

Hom.:

163

Asia WGS

AF:

0.184

AC:

642

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

DANN

Benign

0.60

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