rs9852385

Variant names:

• chr3-41417218-C-T
• rs9852385
• NM_017886.4:c.3493-18954G>A

Variant summary

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

The NM_017886.4(ULK4):​c.3493-18954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,914 control chromosomes in the GnomAD database, including 19,303 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 0.49 (19303 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3493-18954G>A		intron_variant	Intron 34 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3493-18954G>A		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74517 AN: 151796 Hom.: 19277 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.491 AC: 74581 AN: 151914 Hom.: 19303 Cov.: 32 AF XY: 0.483 AC XY: 35846 AN XY: 74228

African (AFR) AF: 0.650 AC: 26926 AN: 41436

American (AMR) AF: 0.421 AC: 6433 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3470

East Asian (EAS) AF: 0.130 AC: 671 AN: 5146

South Asian (SAS) AF: 0.446 AC: 2145 AN: 4810

European-Finnish (FIN) AF: 0.427 AC: 4498 AN: 10522

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30663 AN: 67958

Other (OTH) AF: 0.482 AC: 1013 AN: 2102

Alfa AF: 0.461 Hom.: 28321

Bravo AF: 0.496

Asia WGS AF: 0.350 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.49
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: rs9852385; hg19: chr3-41458709;