3-41443986-T-C

Variant names:

• chr3-41443986-T-C
• rs1495692
• NM_017886.4:c.3492+11511A>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+11511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,938 control chromosomes in the GnomAD database, including 3,640 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 0.20 (3640 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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+11511A>G		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.3492+11511A>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2586+11511A>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+11511A>G		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.3489+11511A>G		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.3408+11511A>G		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30754 AN: 151818 Hom.: 3634 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.203 AC: 30782 AN: 151938 Hom.: 3640 Cov.: 32 AF XY: 0.209 AC XY: 15533 AN XY: 74256

African (AFR) AF: 0.238 AC: 9855 AN: 41438

American (AMR) AF: 0.214 AC: 3259 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2930 AN: 5144

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4826

European-Finnish (FIN) AF: 0.220 AC: 2317 AN: 10546

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10240 AN: 67952

Other (OTH) AF: 0.184 AC: 389 AN: 2114

Alfa AF: 0.166 Hom.: 1145

Bravo AF: 0.208

Asia WGS AF: 0.367 AC: 1267 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.85
PhyloP100		-0.0060
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: rs1495692; hg19: chr3-41485477;