5-111484055-G-C

Variant names:

• chr5-111484055-G-C
• rs25925
• NM_001744.6:c.1011G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001744.6(CAMK4):​c.1011G>C​(p.Ser337Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,599,838 control chromosomes in the GnomAD database, including 500,930 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 0.82 (51941 hom., cov: 32)
  • Exomes 𝑓: 0.78 (448989 hom.)
• Consequence: CAMK4 NM_001744.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 19 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.404 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	NM_001744.6	MANE Select	c.1011G>C	p.Ser337Ser	synonymous	Exon 11 of 11	NP_001735.1
	CAMK4	NM_001323374.2		c.1011G>C	p.Ser337Ser	synonymous	Exon 12 of 12	NP_001310303.1
	CAMK4	NM_001323375.2		c.1011G>C	p.Ser337Ser	synonymous	Exon 12 of 12	NP_001310304.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	ENST00000282356.9	TSL:1 MANE Select	c.1011G>C	p.Ser337Ser	synonymous	Exon 11 of 11	ENSP00000282356.4
	CAMK4	ENST00000512453.5	TSL:1	c.1011G>C	p.Ser337Ser	synonymous	Exon 12 of 12	ENSP00000422634.1
	CAMK4	ENST00000509645.1	TSL:1	n.1020G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124631 AN: 152070 Hom.: 51879 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.786

GnomAD2 exomes AF: 0.750 AC: 178906 AN: 238644 AF XY: 0.748

Gnomad AFR exome AF: 0.948

Gnomad AMR exome AF: 0.649

Gnomad ASJ exome AF: 0.745

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.784 AC: 1135666 AN: 1447650 Hom.: 448989 Cov.: 49 AF XY: 0.780 AC XY: 560994 AN XY: 718924

African (AFR) AF: 0.952 AC: 31598 AN: 33186

American (AMR) AF: 0.659 AC: 28492 AN: 43242

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 18412 AN: 24964

East Asian (EAS) AF: 0.559 AC: 22115 AN: 39590

South Asian (SAS) AF: 0.644 AC: 54025 AN: 83846

European-Finnish (FIN) AF: 0.823 AC: 43464 AN: 52788

Middle Eastern (MID) AF: 0.707 AC: 3975 AN: 5626

European-Non Finnish (NFE) AF: 0.803 AC: 887392 AN: 1104640

Other (OTH) AF: 0.773 AC: 46193 AN: 59768

GnomAD4 genome AF: 0.820 AC: 124754 AN: 152188 Hom.: 51941 Cov.: 32 AF XY: 0.815 AC XY: 60647 AN XY: 74404

African (AFR) AF: 0.947 AC: 39354 AN: 41566

American (AMR) AF: 0.728 AC: 11129 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2589 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2810 AN: 5150

South Asian (SAS) AF: 0.631 AC: 3044 AN: 4822

European-Finnish (FIN) AF: 0.838 AC: 8865 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54484 AN: 67994

Other (OTH) AF: 0.786 AC: 1658 AN: 2110

Alfa AF: 0.803 Hom.: 9908

Bravo AF: 0.817

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		-0.40
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs25925; hg19: chr5-110819753; COSMIC: COSV56685027; COSMIC: COSV56685027;