rs12054016

chr3-41448803-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+6694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,122 control chromosomes in the GnomAD database, including 3,880 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 0.21 (3880 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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=-0.9).
• 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	UniProt
ULK4	NM_017886.4	c.3492+6694G>A		intron_variant		ENST00000301831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.3492+6694G>A		intron_variant		2	NM_017886.4	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31795 AN: 152004 Hom.: 3872 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.209 AC: 31828 AN: 152122 Hom.: 3880 Cov.: 32 AF XY: 0.216 AC XY: 16032 AN XY: 74360

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.195

Alfa AF: 0.176 Hom.: 528

Bravo AF: 0.215

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.57

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: rs12054016; hg19: chr3-41490294;