chr18-59275439-A-G

Position:

• chr18-59275439-A-G

Variant summary

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

The ENST00000587244.5(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 ENST00000587244.5 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]

(HGNC:):

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/exons	MANE	Protein	UniProt
		n.59275439A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLX4	ENST00000587244.5	c.*1257T>C		3_prime_UTR_variant	3/3	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;