rs4973952

Variant names:

• chr3-41483866-G-C
• rs4973952
• NM_017886.4:c.3227-20613C>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.3227-20613C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,970 control chromosomes in the GnomAD database, including 13,494 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 0.42 (13494 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.3227-20613C>G		intron	N/A	NP_060356.2
	ULK4	NM_001322500.2		c.3227-20613C>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2321-20613C>G		intron	N/A	NP_001309430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.3227-20613C>G		intron	N/A	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63494 AN: 151852 Hom.: 13489 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.418 AC: 63524 AN: 151970 Hom.: 13494 Cov.: 31 AF XY: 0.411 AC XY: 30528 AN XY: 74286

African (AFR) AF: 0.464 AC: 19207 AN: 41396

American (AMR) AF: 0.390 AC: 5962 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1491 AN: 3470

East Asian (EAS) AF: 0.171 AC: 885 AN: 5176

South Asian (SAS) AF: 0.407 AC: 1956 AN: 4810

European-Finnish (FIN) AF: 0.385 AC: 4070 AN: 10570

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28559 AN: 67956

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.422 Hom.: 1708

Bravo AF: 0.419

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.14
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: rs4973952; hg19: chr3-41525357;