rs13069584

Positions:

• chr3-41430356-G-A
• chr3-41430356-G-C

Variant summary

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

The NM_017886.4(ULK4):​c.3492+25141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,174 control chromosomes in the GnomAD database, including 998 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 0.11 (998 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK4	NM_017886.4	c.3492+25141C>T		intron_variant		ENST00000301831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.3492+25141C>T		intron_variant		2	NM_017886.4	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15997 AN: 152056 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.105 AC: 16020 AN: 152174 Hom.: 998 Cov.: 32 AF XY: 0.106 AC XY: 7899 AN XY: 74392

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0735 Hom.: 131

Bravo AF: 0.111

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.9
DANN	Benign	0.44

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: rs13069584; hg19: chr3-41471847;