chr5-111231900-C-T

Variant names:

• chr5-111231900-C-T
• rs1457115
• NM_001744.6:c.161+7256C>T

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+7256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,974 control chromosomes in the GnomAD database, including 15,226 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 0.44 (15226 hom., cov: 32)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 15 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.161+7256C>T		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+7256C>T		intron_variant	Intron 1 of 10	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67427 AN: 151856 Hom.: 15218 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.444 AC: 67452 AN: 151974 Hom.: 15226 Cov.: 32 AF XY: 0.439 AC XY: 32620 AN XY: 74274

African (AFR) AF: 0.486 AC: 20132 AN: 41442

American (AMR) AF: 0.365 AC: 5578 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1361 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1259 AN: 5178

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4241 AN: 10534

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31296 AN: 67952

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.456 Hom.: 27037

Bravo AF: 0.445

Asia WGS AF: 0.327 AC: 1139 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		0.17
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: rs1457115; hg19: chr5-110567598;