chr6-35795788-C-T

Variant names:

• chr6-35795788-C-T
• rs113528670
• NM_001832.4:c.150G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001832.4(CLPS):​c.150G>A​(p.Ala50Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,610,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (0 hom., cov: 40)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: CLPS NM_001832.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67
• Publications: 4 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Variant has high frequency in the AFR (0.0517) population. However there is too low homozygotes in high coverage region: (expected more than 6, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-35795788-C-T is Benign according to our data. Variant chr6-35795788-C-T is described in ClinVar as Benign. ClinVar VariationId is 780119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.67 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPS	NM_001832.4	MANE Select	c.150G>A	p.Ala50Ala	synonymous	Exon 2 of 3	NP_001823.1	P04118
	CLPS	NM_001252597.2		c.108G>A	p.Ala36Ala	synonymous	Exon 3 of 4	NP_001239526.1	A0A087WZW1
	CLPS	NM_001252598.2		c.85-511G>A		intron	N/A	NP_001239527.1	A0A087X0Q7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPS	ENST00000259938.7	TSL:1 MANE Select	c.150G>A	p.Ala50Ala	synonymous	Exon 2 of 3	ENSP00000259938.2	P04118
	CLPS	ENST00000616014.3	TSL:1	c.85-511G>A		intron	N/A	ENSP00000483589.1	A0A087X0Q7
	CLPS	ENST00000912425.1		c.150G>A	p.Ala50Ala	synonymous	Exon 3 of 4	ENSP00000582484.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2657 AN: 151460 Hom.: 0 Cov.: 40

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00793

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0197

GnomAD2 exomes AF: 0.00542 AC: 1354 AN: 249594 AF XY: 0.00414

Gnomad AFR exome AF: 0.0493

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0199

Gnomad FIN exome AF: 0.0000956

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00258 AC: 3767 AN: 1459102 Hom.: 0 Cov.: 32 AF XY: 0.00229 AC XY: 1663 AN XY: 725882

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

African (AFR) AF: 0.0538 AC: 1763 AN: 32782

American (AMR) AF: 0.00401 AC: 179 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0290 AC: 1132 AN: 39018

South Asian (SAS) AF: 0.00117 AC: 101 AN: 86170

European-Finnish (FIN) AF: 0.000286 AC: 15 AN: 52468

Middle Eastern (MID) AF: 0.00538 AC: 31 AN: 5760

European-Non Finnish (NFE) AF: 0.000142 AC: 158 AN: 1111920

Other (OTH) AF: 0.00644 AC: 388 AN: 60208

⚠️ 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 AF: 0.0176 AC: 2661 AN: 151576 Hom.: 0 Cov.: 40 AF XY: 0.0168 AC XY: 1242 AN XY: 74126

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

African (AFR) AF: 0.0567 AC: 2321 AN: 40922

American (AMR) AF: 0.00792 AC: 121 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0249 AC: 127 AN: 5106

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68042

Other (OTH) AF: 0.0210 AC: 44 AN: 2100

⚠️ 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: 0.00434 Hom.: 0

Asia WGS AF: 0.0380 AC: 131 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113528670; hg19: chr6-35763565; COSMIC: COSV52566107; COSMIC: COSV52566107;