rs583241

chr18-59311623-A-T

Variant summary

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

The NM_181654.4(CPLX4):c.255+1062T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,984 control chromosomes in the GnomAD database, including 6,604 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 0.29 (6604 hom., cov: 31)
• Consequence: CPLX4 NM_181654.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX4	NM_181654.4	c.255+1062T>A		intron_variant		ENST00000299721.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLX4	ENST00000299721.3	c.255+1062T>A		intron_variant		1	NM_181654.4	P1
CPLX4	ENST00000587244.5	c.255+1062T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44710 AN: 151866 Hom.: 6602 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44721 AN: 151984 Hom.: 6604 Cov.: 31 AF XY: 0.298 AC XY: 22140 AN XY: 74304

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.308

Alfa AF: 0.288 Hom.: 780

Bravo AF: 0.292

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.85

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: rs583241; hg19: chr18-56978855;