rs10491334

Variant names:

• chr5-111436706-C-T
• rs10491334
• NM_001744.6:c.460-9980C>T

Variant summary

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

The NM_001744.6(CAMK4):​c.460-9980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,192 control chromosomes in the GnomAD database, including 1,635 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 0.14 (1635 hom., cov: 32)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 44 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 = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.460-9980C>T		intron_variant	Intron 5 of 10	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.460-9980C>T		intron_variant	Intron 5 of 10	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20954 AN: 152072 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.138 AC: 20965 AN: 152192 Hom.: 1635 Cov.: 32 AF XY: 0.132 AC XY: 9835 AN XY: 74430

African (AFR) AF: 0.0680 AC: 2823 AN: 41526

American (AMR) AF: 0.145 AC: 2209 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3468

East Asian (EAS) AF: 0.0540 AC: 280 AN: 5184

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1288 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12969 AN: 67992

Other (OTH) AF: 0.173 AC: 366 AN: 2112

Alfa AF: 0.168 Hom.: 5675

Bravo AF: 0.141

Asia WGS AF: 0.0570 AC: 197 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	1.4
DANN	Benign	0.42
PhyloP100		-0.31
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: rs10491334; hg19: chr5-110772404; COSMIC: COSV56682601;