rs77636885

Variant names:

• chr5-111383489-C-A
• rs77636885
• NM_001744.6:c.386+6547C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001744.6(CAMK4):​c.386+6547C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 152,280 control chromosomes in the GnomAD database, including 58 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 0.020 (58 hom., cov: 32)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 8 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0203 (3085/152280) while in subpopulation NFE AF = 0.0315 (2145/68028). AF 95% confidence interval is 0.0304. There are 58 homozygotes in GnomAd4. There are 1476 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3085 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	NM_001744.6	MANE Select	c.386+6547C>A		intron	N/A	NP_001735.1	Q16566
	CAMK4	NM_001323374.2		c.386+6547C>A		intron	N/A	NP_001310303.1	Q16566
	CAMK4	NM_001323375.2		c.386+6547C>A		intron	N/A	NP_001310304.1	Q16566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	ENST00000282356.9	TSL:1 MANE Select	c.386+6547C>A		intron	N/A	ENSP00000282356.4	Q16566
	CAMK4	ENST00000512453.5	TSL:1	c.386+6547C>A		intron	N/A	ENSP00000422634.1	Q16566
	CAMK4	ENST00000515231.5	TSL:1	n.241-11221C>A		intron	N/A	ENSP00000424912.1	D6RCD6

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3083 AN: 152162 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0203 AC: 3085 AN: 152280 Hom.: 58 Cov.: 32 AF XY: 0.0198 AC XY: 1476 AN XY: 74442

African (AFR) AF: 0.00695 AC: 289 AN: 41554

American (AMR) AF: 0.0120 AC: 184 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4824

European-Finnish (FIN) AF: 0.0321 AC: 341 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2145 AN: 68028

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0272 Hom.: 117

Bravo AF: 0.0183

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.0050
Mutation Taster		=100/0	polymorphism

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: rs77636885; hg19: chr5-110719187;