rs12232751

chr18-59299028-G-A

Variant summary

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

The NM_181654.4(CPLX4):c.256-2103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,214 control chromosomes in the GnomAD database, including 5,006 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 0.25 (5006 hom., cov: 33)
• Consequence: CPLX4 NM_181654.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX4	NM_181654.4	c.256-2103C>T		intron_variant		ENST00000299721.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLX4	ENST00000299721.3	c.256-2103C>T		intron_variant		1	NM_181654.4	P1
CPLX4	ENST00000587244.5	c.255+13657C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37557 AN: 152096 Hom.: 5007 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.247 AC: 37552 AN: 152214 Hom.: 5006 Cov.: 33 AF XY: 0.253 AC XY: 18834 AN XY: 74408

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.274

Alfa AF: 0.256 Hom.: 671

Bravo AF: 0.235

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.22
Dann	Benign	0.73

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: rs12232751; hg19: chr18-56966260;