rs13059459

Positions:

• chr3-41451139-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017886.4(ULK4):​c.3492+4358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,854 control chromosomes in the GnomAD database, including 5,291 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 0.26 (5291 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

ULK4 (HGNC:15784): (unc-51 like kinase 4) This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+4358G>A		intron_variant		ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3492+4358G>A		intron_variant		2	NM_017886.4	ENSP00000301831	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39083 AN: 151736 Hom.: 5283 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.258 AC: 39117 AN: 151854 Hom.: 5291 Cov.: 31 AF XY: 0.262 AC XY: 19420 AN XY: 74176

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.246

Alfa AF: 0.236 Hom.: 4513

Bravo AF: 0.260

Asia WGS AF: 0.382 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs13059459; hg19: chr3-41492630;