rs2766595

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-35796793-G-A
• chr6-35796793-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• 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: Benign. The variant received -10 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 VariationId is 402546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 145 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPS	NM_001832.4	c.84+412C>T		intron_variant	Intron 1 of 2	ENST00000259938.7	NP_001823.1
CLPS	NM_001252597.2	c.42+16C>T		intron_variant	Intron 2 of 3		NP_001239526.1
CLPS	NM_001252598.2	c.84+412C>T		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>T		intron_variant	Intron 1 of 2	1	NM_001832.4	ENSP00000259938.2
CLPS	ENST00000616014.3	c.84+412C>T		intron_variant	Intron 1 of 1	1		ENSP00000483589.1
CLPS	ENST00000622413.2	c.42+16C>T		intron_variant	Intron 1 of 2	5		ENSP00000482919.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 36841 AN: 146996 Hom.: 482 Cov.: 45

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

GnomAD2 exomes AF: 0.142 AC: 15003 AN: 105302 AF XY: 0.138

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.336 AC: 2310 AN: 6884

American (AMR) AF: 0.114 AC: 2679 AN: 23438

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1289 AN: 9286

East Asian (EAS) AF: 0.198 AC: 1561 AN: 7870

South Asian (SAS) AF: 0.110 AC: 5697 AN: 51604

European-Finnish (FIN) AF: 0.135 AC: 1405 AN: 10444

Middle Eastern (MID) AF: 0.215 AC: 201 AN: 936

European-Non Finnish (NFE) AF: 0.159 AC: 21377 AN: 134390

Other (OTH) AF: 0.172 AC: 2038 AN: 11866

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.368 AC: 14806 AN: 40202

American (AMR) AF: 0.209 AC: 3097 AN: 14850

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 651 AN: 3384

East Asian (EAS) AF: 0.244 AC: 1239 AN: 5078

South Asian (SAS) AF: 0.158 AC: 740 AN: 4682

European-Finnish (FIN) AF: 0.180 AC: 1823 AN: 10126

Middle Eastern (MID) AF: 0.270 AC: 76 AN: 282

European-Non Finnish (NFE) AF: 0.210 AC: 13765 AN: 65598

Other (OTH) AF: 0.256 AC: 520 AN: 2032

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.97
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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