rs1495698

Variant names:

• chr3-41491059-T-C
• rs1495698
• NM_017886.4:c.3227-27806A>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.3227-27806A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,008 control chromosomes in the GnomAD database, including 7,594 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 0.31 (7594 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 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.3227-27806A>G		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.3227-27806A>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2321-27806A>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.3227-27806A>G		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.3224-27806A>G		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.3143-27806A>G		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47339 AN: 151890 Hom.: 7594 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.311 AC: 47339 AN: 152008 Hom.: 7594 Cov.: 32 AF XY: 0.304 AC XY: 22551 AN XY: 74298

African (AFR) AF: 0.318 AC: 13177 AN: 41466

American (AMR) AF: 0.246 AC: 3751 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.123 AC: 635 AN: 5178

South Asian (SAS) AF: 0.316 AC: 1522 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2807 AN: 10542

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22981 AN: 67962

Other (OTH) AF: 0.337 AC: 712 AN: 2112

Alfa AF: 0.333 Hom.: 13816

Bravo AF: 0.308

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.54
DANN	Benign	0.70
PhyloP100		-0.18
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1495698;

hg19: chr3-41532550;