Genetic Variant NM_001828.6:c.240T>C (chr19-39734346-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001828.6(CLC):c.240T>C(p.Asn80Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,613,720 control chromosomes in the GnomAD database, including 355,216 homozygotes. 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: 𝑓 0.67 ( 34656 hom., cov: 31)

Exomes 𝑓: 0.66 ( 320560 hom. )

Consequence

CLC
NM_001828.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.09).

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLC	NM_001828.6 link	c.240T>C	p.Asn80Asn	synonymous_variant	Exon 3 of 4	ENST00000221804.5	NP_001819.2	Q05315

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLC	ENST00000221804.5 link	c.240T>C	p.Asn80Asn	synonymous_variant	Exon 3 of 4	1	NM_001828.6	ENSP00000221804.3		Q05315

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101472

AN:

151922

Hom.:

34613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.621

GnomAD2 exomes

AF:

0.615

AC:

154220

AN:

250866

AF XY:

0.625

show subpopulations

Gnomad AFR exome

AF:

0.767

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.694

Gnomad EAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.688

Gnomad NFE exome

AF:

0.669

Gnomad OTH exome

AF:

0.626

GnomAD4 exome

AF:

0.658

AC:

961066

AN:

1461680

Hom.:

320560

Cov.:

AF XY:

0.659

AC XY:

479277

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.769

AC:

25727

AN:

33474

American (AMR)

AF:

0.404

AC:

18069

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.694

AC:

18128

AN:

26136

East Asian (EAS)

AF:

0.379

AC:

15062

AN:

39692

South Asian (SAS)

AF:

0.684

AC:

59039

AN:

86258

European-Finnish (FIN)

AF:

0.691

AC:

36870

AN:

53370

Middle Eastern (MID)

AF:

0.660

AC:

3805

AN:

5768

European-Non Finnish (NFE)

AF:

0.670

AC:

745172

AN:

1111872

Other (OTH)

AF:

0.649

AC:

39194

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

19009

38017

57026

76034

95043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.668

AC:

101556

AN:

152040

Hom.:

34656

Cov.:

AF XY:

0.663

AC XY:

49243

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.764

AC:

31678

AN:

41484

American (AMR)

AF:

0.497

AC:

7586

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

2419

AN:

3472

East Asian (EAS)

AF:

0.341

AC:

1758

AN:

5154

South Asian (SAS)

AF:

0.672

AC:

3234

AN:

4816

European-Finnish (FIN)

AF:

0.692

AC:

7307

AN:

10556

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45573

AN:

67964

Other (OTH)

AF:

0.615

AC:

1298

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1671

3341

5012

6682

8353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.668

Hom.:

29414

Bravo

AF:

0.651

Asia WGS

AF:

0.509

AC:

1771

AN:

3476

EpiCase

AF:

0.660

EpiControl

AF:

0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.64

(source)

DANN

Benign

0.24

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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NM_001828.6:c.240T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over