Variant chr19-39734391-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001828.6(CLC):c.195C>G(p.Asn65Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,614,070 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 42 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 266 hom. )

Consequence

CLC
NM_001828.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

CLC (HGNC:2014): (Charcot-Leyden crystal galectin) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene is a lysophospholipase expressed in eosinophils and basophils. It hydrolyzes lysophosphatidylcholine to glycerophosphocholine and a free fatty acid. This protein may possess carbohydrate or IgE-binding activities. It is both structurally and functionally related to the galectin family of beta-galactoside binding proteins. It may be associated with inflammation and some myeloid leukemias. [provided by RefSeq, Jul 2008]

CLC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013160795).

BP6

Variant 19-39734391-G-C is Benign according to our data. Variant chr19-39734391-G-C is described in ClinVar as [Benign]. Clinvar id is 1237360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLC	NM_001828.6 linkuse as main transcript	c.195C>G	p.Asn65Lys	missense_variant	3/4	ENST00000221804.5	NP_001819.2	Q05315

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLC	ENST00000221804.5 linkuse as main transcript	c.195C>G	p.Asn65Lys	missense_variant	3/4	1	NM_001828.6	ENSP00000221804.3		Q05315

Frequencies

GnomAD3 genomes

AF:

0.00993

AC:

1511

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0395

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0178

AC:

4476

AN:

250946

Hom.:

156

AF XY:

0.0157

AC XY:

2125

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0771

Gnomad ASJ exome

AF:

0.00805

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.00727

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.00924

AC:

13502

AN:

1461776

Hom.:

266

Cov.:

AF XY:

0.00893

AC XY:

6491

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0770

Gnomad4 ASJ exome

AF:

0.00796

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.00641

Gnomad4 OTH exome

AF:

0.00979

GnomAD4 genome

AF:

0.00992

AC:

1510

AN:

152294

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

815

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0275

Gnomad4 NFE

AF:

0.00660

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00677

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.0156

AC:

1896

Asia WGS

AF:

0.00578

AC:

AN:

3476

EpiCase

AF:

0.00638

EpiControl

AF:

0.00658

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2020	This variant is associated with the following publications: (PMID: 29884787) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

0.041

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.77

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.17

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.27

MutPred

0.94

Gain of catalytic residue at N65 (P = 0.0252);

MPC

0.57

ClinPred

0.12

GERP RS

1.3

Varity_R

0.84

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over