5-111397942-T-C

Variant names:

• chr5-111397942-T-C
• rs17133238
• NM_001744.6:c.459+3160T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001744.6(CAMK4):​c.459+3160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,986 control chromosomes in the GnomAD database, including 8,133 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 0.30 (8133 hom., cov: 31)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

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+3160T>C		intron	N/A	NP_001735.1
	CAMK4	NM_001323374.2		c.459+3160T>C		intron	N/A	NP_001310303.1
	CAMK4	NM_001323375.2		c.459+3160T>C		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+3160T>C		intron	N/A	ENSP00000282356.4
	CAMK4	ENST00000512453.5	TSL:1	c.459+3160T>C		intron	N/A	ENSP00000422634.1
	CAMK4	ENST00000515231.5	TSL:1	n.*46+3160T>C		intron	N/A	ENSP00000424912.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45127 AN: 151868 Hom.: 8129 Cov.: 31

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.297 AC: 45138 AN: 151986 Hom.: 8133 Cov.: 31 AF XY: 0.297 AC XY: 22047 AN XY: 74272

African (AFR) AF: 0.0845 AC: 3505 AN: 41498

American (AMR) AF: 0.378 AC: 5757 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1538 AN: 5158

South Asian (SAS) AF: 0.309 AC: 1493 AN: 4824

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26879 AN: 67918

Other (OTH) AF: 0.328 AC: 693 AN: 2110

Alfa AF: 0.269 Hom.: 1026

Bravo AF: 0.291

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		0.49
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: rs17133238; hg19: chr5-110733640; COSMIC: COSV56682532; COSMIC: COSV56682532;