rs9852991

Variant names:

• chr3-41833963-C-A
• rs9852991
• NM_017886.4:c.1764+1901G>T

Variant summary

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

The NM_017886.4(ULK4):​c.1764+1901G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,810 control chromosomes in the GnomAD database, including 2,608 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 0.18 (2608 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 11 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.1764+1901G>T		intron_variant	Intron 18 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1764+1901G>T		intron_variant	Intron 18 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000460406.1	n.245+1901G>T		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27711 AN: 151694 Hom.: 2604 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.183 AC: 27719 AN: 151810 Hom.: 2608 Cov.: 32 AF XY: 0.185 AC XY: 13736 AN XY: 74170

African (AFR) AF: 0.206 AC: 8541 AN: 41378

American (AMR) AF: 0.156 AC: 2381 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.166 AC: 861 AN: 5182

South Asian (SAS) AF: 0.185 AC: 892 AN: 4812

European-Finnish (FIN) AF: 0.225 AC: 2354 AN: 10468

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

European-Non Finnish (NFE) AF: 0.168 AC: 11390 AN: 67958

Other (OTH) AF: 0.198 AC: 417 AN: 2108

Alfa AF: 0.172 Hom.: 295

Bravo AF: 0.178

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		0.19
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: rs9852991; hg19: chr3-41875455;