5-111232760-T-C

Variant names:

• chr5-111232760-T-C
• rs9285875
• NM_001744.6:c.161+8116T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001744.6(CAMK4):​c.161+8116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 151,650 control chromosomes in the GnomAD database, including 46,225 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 0.78 (46225 hom., cov: 29)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.161+8116T>C		intron_variant	Intron 1 of 10	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.161+8116T>C		intron_variant	Intron 1 of 10	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117584 AN: 151532 Hom.: 46163 Cov.: 29

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.776 AC: 117705 AN: 151650 Hom.: 46225 Cov.: 29 AF XY: 0.774 AC XY: 57305 AN XY: 74054

African (AFR) AF: 0.900 AC: 37324 AN: 41462

American (AMR) AF: 0.773 AC: 11777 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2255 AN: 3464

East Asian (EAS) AF: 0.603 AC: 3111 AN: 5156

South Asian (SAS) AF: 0.730 AC: 3504 AN: 4800

European-Finnish (FIN) AF: 0.688 AC: 7161 AN: 10406

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50003 AN: 67816

Other (OTH) AF: 0.755 AC: 1587 AN: 2102

Alfa AF: 0.746 Hom.: 138419

Bravo AF: 0.785

Asia WGS AF: 0.691 AC: 2396 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-1.3
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: rs9285875; hg19: chr5-110568458;