rs41270082

chr6-35795160-G-Achr6-35795160-G-Cchr6-35795160-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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]

ACMG classification

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	UniProt
CLPS	NM_001832.4	c.325C>T	p.Arg109Cys	missense_variant	3/3	ENST00000259938.7
CLPS	NM_001252597.2	c.283C>T	p.Arg95Cys	missense_variant	4/4
CLPS	NM_001252598.2	c.202C>T	p.Arg68Cys	missense_variant	2/2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1046 AN: 151944 Hom.: 0 Cov.: 40

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.: 0 AF XY: 0.00874 AC XY: 1183 AN XY: 135314

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.: 0 Cov.: 31 AF XY: 0.00940 AC XY: 6808 AN XY: 724452

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.: 0 Cov.: 40 AF XY: 0.00708 AC XY: 526 AN XY: 74332

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.: 0

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0110 AC: 95

ExAC AF: 0.0115 AC: 1398

Asia WGS AF: 0.00577 AC: 20 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	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.11	T;D;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.76	T;T;T
MetaRNN	Benign	0.0065	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.0010	.;B;.
Vest4		0.13
MPC		1.1
ClinPred		0.042	T
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

Other links and lift over

dbSNP: rs41270082; hg19: chr6-35762937;