chr18-59311623-A-T

Variant names:

• chr18-59311623-A-T
• rs583241
• NM_181654.4:c.255+1062T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181654.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX4	NM_181654.4	MANE Select	c.255+1062T>A		intron	N/A	NP_857637.1	Q7Z7G2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX4	ENST00000299721.3	TSL:1 MANE Select	c.255+1062T>A		intron	N/A	ENSP00000299721.3	Q7Z7G2
	CPLX4	ENST00000587244.5	TSL:1	c.255+1062T>A		intron	N/A	ENSP00000466304.1	K7EM04

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

African (AFR) AF: 0.289 AC: 11985 AN: 41462

American (AMR) AF: 0.306 AC: 4677 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3466

East Asian (EAS) AF: 0.274 AC: 1408 AN: 5144

South Asian (SAS) AF: 0.351 AC: 1691 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3481 AN: 10560

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19227 AN: 67948

Other (OTH) AF: 0.308 AC: 649 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.85
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs583241; hg19: chr18-56978855;