chr18-59275439-A-G

Variant names:

• chr18-59275439-A-G
• rs3760559
• ENST00000587244.5:c.*1257T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587244.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX4	ENST00000587244.5	TSL:1	c.*1257T>C		3_prime_UTR	Exon 3 of 3	ENSP00000466304.1	K7EM04

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.350 AC: 14 AN: 40

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.374 AC: 15504 AN: 41474

American (AMR) AF: 0.290 AC: 4440 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3472

East Asian (EAS) AF: 0.148 AC: 764 AN: 5172

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2431 AN: 10596

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23350 AN: 67996

Other (OTH) AF: 0.319 AC: 673 AN: 2112

Alfa AF: 0.334 Hom.: 4512

Bravo AF: 0.332

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.58
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3760559;

hg19: chr18-56942671;