chr6-35796793-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPS	NM_001832.4	c.84+412C>G		intron_variant	Intron 1 of 2	ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2	c.42+16C>G		intron_variant	Intron 2 of 3		NP_001239526.1
CLPS	NM_001252598.2	c.84+412C>G		intron_variant	Intron 1 of 1		NP_001239527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPS	ENST00000259938.7	c.84+412C>G		intron_variant	Intron 1 of 2	1	NM_001832.4	ENSP00000259938.2
CLPS	ENST00000616014.3	c.84+412C>G		intron_variant	Intron 1 of 1	1		ENSP00000483589.1
CLPS	ENST00000622413.2	c.42+16C>G		intron_variant	Intron 1 of 2	5		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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000643

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	15
DANN	Benign	0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35764570;