rs2300782

Variant names:

• chr5-111453087-C-T
• rs2300782
• NM_001744.6:c.625+3884C>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.625+3884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,036 control chromosomes in the GnomAD database, including 10,478 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 0.35 (10478 hom., cov: 32)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.625+3884C>T		intron_variant	Intron 7 of 10	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.625+3884C>T		intron_variant	Intron 7 of 10	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52794 AN: 151918 Hom.: 10481 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.347 AC: 52794 AN: 152036 Hom.: 10478 Cov.: 32 AF XY: 0.348 AC XY: 25893 AN XY: 74310

African (AFR) AF: 0.149 AC: 6165 AN: 41466

American (AMR) AF: 0.381 AC: 5828 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2325 AN: 5180

South Asian (SAS) AF: 0.407 AC: 1959 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4364 AN: 10546

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29145 AN: 67966

Other (OTH) AF: 0.370 AC: 781 AN: 2108

Alfa AF: 0.371 Hom.: 1482

Bravo AF: 0.334

Asia WGS AF: 0.378 AC: 1314 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.68
PhyloP100		-0.26
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: rs2300782; hg19: chr5-110788785; COSMIC: COSV56666939; COSMIC: COSV56666939;