rs384138

chr19-39734346-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001828.6(CLC):c.240T>C(p.Asn80=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CLC	NM_001828.6	c.240T>C	p.Asn80=	synonymous_variant	3/4	ENST00000221804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLC	ENST00000221804.5	c.240T>C	p.Asn80=	synonymous_variant	3/4	1	NM_001828.6	P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101472 AN: 151922 Hom.: 34613 Cov.: 31

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

GnomAD3 exomes AF: 0.615 AC: 154220 AN: 250866 Hom.: 50067 AF XY: 0.625 AC XY: 84667 AN XY: 135550

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 SAS exome AF: 0.687

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.: 60 AF XY: 0.659 AC XY: 479277 AN XY: 727138

Gnomad4 AFR exome AF: 0.769

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.649

GnomAD4 genome AF: 0.668 AC: 101556 AN: 152040 Hom.: 34656 Cov.: 31 AF XY: 0.663 AC XY: 49243 AN XY: 74300

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.615

Alfa AF: 0.677 Hom.: 19282

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
Dann	Benign	0.24

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

LitVar

Other links and lift over

dbSNP: rs384138; hg19: chr19-40224986; COSMIC: COSV55684660;