18-59275439-A-G

Variant names:

• chr18-59275439-A-G
• rs3760559
• ENST00000587244:c.*1257T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000587244(CPLX4):​c.*1257T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,200 control chromosomes in the GnomAD database, including 8,581 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 0.33 (8574 hom., cov: 33)
  • Exomes 𝑓: 0.36 (7 hom.)
• Consequence: CPLX4 ENST00000587244 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

Genes affected

CPLX4 (HGNC:24330): (complexin 4) This gene likely encodes a member of the complexin family. The encoded protein may be involved in synaptic vesicle exocytosis. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLX4	ENST00000587244	c.*1257T>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000466304.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49821 AN: 152024 Hom.: 8549 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.362 AC: 21 AN: 58 Hom.: 7 Cov.: 0 AF XY: 0.364 AC XY: 16 AN XY: 44

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.328 AC: 49889 AN: 152142 Hom.: 8574 Cov.: 33 AF XY: 0.319 AC XY: 23742 AN XY: 74378

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.319

Alfa AF: 0.332 Hom.: 3994

Bravo AF: 0.332

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3760559; hg19: chr18-56942671;