5-111484055-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001744.6(CAMK4):c.1011G>C(p.Ser337=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK4	NM_001744.6	c.1011G>C	p.Ser337=	synonymous_variant	11/11	ENST00000282356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK4	ENST00000282356.9	c.1011G>C	p.Ser337=	synonymous_variant	11/11	1	NM_001744.6	P1

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

GnomAD3 exomes AF: 0.750 AC: 178906 AN: 238644 Hom.: 68439 AF XY: 0.748 AC XY: 96405 AN XY: 128818

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 SAS exome AF: 0.642

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

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.773

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

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.786

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	7.9
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs25925; hg19: chr5-110819753; COSMIC: COSV56685027; COSMIC: COSV56685027;