Genetic Variant CAMK4:c.459+77C>T (chr5-111394859-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001744.6(CAMK4):c.459+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 889,060 control chromosomes in the GnomAD database, including 368,231 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 0.91 ( 62913 hom., cov: 30)

Exomes 𝑓: 0.91 ( 305318 hom. )

Consequence

CAMK4
NM_001744.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Publications

5 publications found

Variant links:

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

CAMK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMK4	NM_001744.6	MANE Select	c.459+77C>T	intron	N/A	NP_001735.1	Q16566
CAMK4	NM_001323374.2		c.459+77C>T	intron	N/A	NP_001310303.1	Q16566
CAMK4	NM_001323375.2		c.459+77C>T	intron	N/A	NP_001310304.1	Q16566

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMK4	ENST00000282356.9	TSL:1 MANE Select	c.459+77C>T	intron	N/A	ENSP00000282356.4	Q16566
CAMK4	ENST00000512453.5	TSL:1	c.459+77C>T	intron	N/A	ENSP00000422634.1	Q16566
CAMK4	ENST00000515231.5	TSL:1	n.*46+77C>T	intron	N/A	ENSP00000424912.1	D6RCD6

Frequencies

GnomAD3 genomes

AF:

0.909

AC:

138125

AN:

151942

Hom.:

62868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.908

Gnomad ASJ

AF:

0.933

Gnomad EAS

AF:

0.990

Gnomad SAS

AF:

0.979

Gnomad FIN

AF:

0.935

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.896

GnomAD4 exome

AF:

0.909

AC:

670236

AN:

737000

Hom.:

305318

AF XY:

0.912

AC XY:

357351

AN XY:

391658

show subpopulations

African (AFR)

AF:

0.916

AC:

17376

AN:

18978

American (AMR)

AF:

0.940

AC:

36453

AN:

38768

Ashkenazi Jewish (ASJ)

AF:

0.937

AC:

19374

AN:

20666

East Asian (EAS)

AF:

0.991

AC:

35186

AN:

35520

South Asian (SAS)

AF:

0.975

AC:

65782

AN:

67482

European-Finnish (FIN)

AF:

0.927

AC:

48294

AN:

52118

Middle Eastern (MID)

AF:

0.876

AC:

3777

AN:

4314

European-Non Finnish (NFE)

AF:

0.888

AC:

411246

AN:

462890

Other (OTH)

AF:

0.903

AC:

32748

AN:

36264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2873

5747

8620

11494

14367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4622

9244

13866

18488

23110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.909

AC:

138229

AN:

152060

Hom.:

62913

Cov.:

AF XY:

0.912

AC XY:

67744

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.917

AC:

38030

AN:

41466

American (AMR)

AF:

0.908

AC:

13830

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.933

AC:

3236

AN:

3470

East Asian (EAS)

AF:

0.990

AC:

5124

AN:

5174

South Asian (SAS)

AF:

0.979

AC:

4720

AN:

4822

European-Finnish (FIN)

AF:

0.935

AC:

9898

AN:

10582

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.890

AC:

60553

AN:

68004

Other (OTH)

AF:

0.897

AC:

1894

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

635

1270

1904

2539

3174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.903

Hom.:

9793

Bravo

AF:

0.906

Asia WGS

AF:

0.972

AC:

3380

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.90

(source)

DANN

Benign

0.44

PhyloP100

-0.92

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over