6-35796793-G-A

Position:

• chr6-35796793-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.968

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 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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPS	NM_001832.4	c.84+412C>T		intron_variant		ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2	c.42+16C>T		intron_variant			NP_001239526.1
CLPS	NM_001252598.2	c.84+412C>T		intron_variant			NP_001239527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPS	ENST00000259938.7	c.84+412C>T		intron_variant		1	NM_001832.4	ENSP00000259938.2
CLPS	ENST00000616014.3	c.84+412C>T		intron_variant		1		ENSP00000483589.1
CLPS	ENST00000622413.2	c.42+16C>T		intron_variant		5		ENSP00000482919.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 36841 AN: 146996 Hom.: 482 Cov.: 45 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.: 77 AF XY: 0.138 AC XY: 7978 AN XY: 57726

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.: 0 AF XY: 0.145 AC XY: 21348 AN XY: 146842

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.: 45 AF XY: 0.247 AC XY: 17782 AN XY: 71888

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.: 37

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Other links and lift over

dbSNP: rs2766595; hg19: chr6-35764570; COSMIC: COSV52567121; COSMIC: COSV52567121;