rs6599155

Variant names:

• chr3-41448113-A-C
• rs6599155
• NM_017886.4:c.3492+7384T>G

Variant summary

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

The NM_017886.4(ULK4):​c.3492+7384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,076 control chromosomes in the GnomAD database, including 8,164 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 0.32 (8164 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 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.3492+7384T>G		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.3492+7384T>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2586+7384T>G		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.3492+7384T>G		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.3489+7384T>G		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.3408+7384T>G		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48931 AN: 151958 Hom.: 8153 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.322 AC: 48954 AN: 152076 Hom.: 8164 Cov.: 32 AF XY: 0.316 AC XY: 23504 AN XY: 74348

African (AFR) AF: 0.391 AC: 16227 AN: 41476

American (AMR) AF: 0.227 AC: 3472 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3472

East Asian (EAS) AF: 0.119 AC: 614 AN: 5178

South Asian (SAS) AF: 0.317 AC: 1524 AN: 4808

European-Finnish (FIN) AF: 0.306 AC: 3235 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21660 AN: 67960

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.316 Hom.: 25851

Bravo AF: 0.317

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.12
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: rs6599155; hg19: chr3-41489604;