rs9834824

Variant names:

• chr3-41491611-A-G
• rs9834824
• NM_017886.4:c.3227-28358T>C

Variant summary

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

The NM_017886.4(ULK4):​c.3227-28358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,946 control chromosomes in the GnomAD database, including 12,994 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 0.41 (12994 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 1 publications found

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]

ULK4 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.3227-28358T>C		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.3227-28358T>C		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2321-28358T>C		intron	N/A	NP_001309430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.3227-28358T>C		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.3224-28358T>C		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.3143-28358T>C		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62363 AN: 151828 Hom.: 12989 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.411 AC: 62387 AN: 151946 Hom.: 12994 Cov.: 32 AF XY: 0.404 AC XY: 29976 AN XY: 74278

African (AFR) AF: 0.437 AC: 18098 AN: 41430

American (AMR) AF: 0.387 AC: 5917 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3466

East Asian (EAS) AF: 0.164 AC: 846 AN: 5172

South Asian (SAS) AF: 0.391 AC: 1885 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4045 AN: 10512

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28713 AN: 67960

Other (OTH) AF: 0.421 AC: 887 AN: 2108

Alfa AF: 0.415 Hom.: 2306

Bravo AF: 0.410

Asia WGS AF: 0.316 AC: 1098 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.59
PhyloP100		1.9
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: rs9834824; hg19: chr3-41533102;