6-35796793-G-C

Variant names:

• chr6-35796793-G-C
• rs2766595
• NM_001832.4:c.84+412C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001832.4(CLPS):​c.84+412C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 292,734 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.

• Frequency:
  • Genomes: not found (cov: 45)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CLPS NM_001832.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001832.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPS	NM_001832.4	MANE Select	c.84+412C>G		intron	N/A	NP_001823.1
	CLPS	NM_001252597.2		c.42+16C>G		intron	N/A	NP_001239526.1
	CLPS	NM_001252598.2		c.84+412C>G		intron	N/A	NP_001239527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPS	ENST00000259938.7	TSL:1 MANE Select	c.84+412C>G		intron	N/A	ENSP00000259938.2
	CLPS	ENST00000616014.3	TSL:1	c.84+412C>G		intron	N/A	ENSP00000483589.1
	CLPS	ENST00000622413.2	TSL:5	c.42+16C>G		intron	N/A	ENSP00000482919.1

Frequencies

GnomAD3 genomes Cov.: 45

GnomAD4 exome AF: 0.00000342 AC: 1 AN: 292734 Hom.: 0 Cov.: 0 AF XY: 0.00000599 AC XY: 1 AN XY: 166988

African (AFR) AF: 0.00 AC: 0 AN: 7918

American (AMR) AF: 0.00 AC: 0 AN: 25616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10490

East Asian (EAS) AF: 0.00 AC: 0 AN: 8822

South Asian (SAS) AF: 0.00 AC: 0 AN: 57626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1100

European-Non Finnish (NFE) AF: 0.00000643 AC: 1 AN: 155426

Other (OTH) AF: 0.00 AC: 0 AN: 13646

GnomAD4 genome Cov.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	15
DANN	Benign	0.66
PhyloP100		0.97
PromoterAI		-0.018	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2766595; hg19: chr6-35764570;