rs523389

Variant names:

• chr5-111394859-C-A
• rs523389
• NM_001744.6:c.459+77C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-111394859-C-A
• chr5-111394859-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001744.6(CAMK4):​c.459+77C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 5 publications found

Genes affected

CAMK4 (HGNC:1464): (calcium/calmodulin dependent protein kinase IV) The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

CAMK4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001744.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	NM_001744.6	MANE Select	c.459+77C>A		intron	N/A	NP_001735.1
	CAMK4	NM_001323374.2		c.459+77C>A		intron	N/A	NP_001310303.1
	CAMK4	NM_001323375.2		c.459+77C>A		intron	N/A	NP_001310304.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	ENST00000282356.9	TSL:1 MANE Select	c.459+77C>A		intron	N/A	ENSP00000282356.4
	CAMK4	ENST00000512453.5	TSL:1	c.459+77C>A		intron	N/A	ENSP00000422634.1
	CAMK4	ENST00000515231.5	TSL:1	n.*46+77C>A		intron	N/A	ENSP00000424912.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 737570 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 391922

African (AFR) AF: 0.00 AC: 0 AN: 18990

American (AMR) AF: 0.00 AC: 0 AN: 38782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20666

East Asian (EAS) AF: 0.00 AC: 0 AN: 35520

South Asian (SAS) AF: 0.00 AC: 0 AN: 67500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 463374

Other (OTH) AF: 0.00 AC: 0 AN: 36298

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-0.92

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: rs523389; hg19: chr5-110730557;