3-41318417-G-T

Variant names:

• chr3-41318417-G-T
• rs6789086
• NM_017886.4:c.3679-68843C>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.3679-68843C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,168 control chromosomes in the GnomAD database, including 1,228 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 0.080 (1228 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 0 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 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.3679-68843C>A		intron	N/A	NP_060356.2
	ULK4	NM_001322501.2		c.2773-68843C>A		intron	N/A	NP_001309430.1
	ULK4	NR_136342.2		n.3650-68843C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.3679-68843C>A		intron	N/A	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12153 AN: 152050 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0801 AC: 12183 AN: 152168 Hom.: 1228 Cov.: 32 AF XY: 0.0809 AC XY: 6021 AN XY: 74390

African (AFR) AF: 0.229 AC: 9482 AN: 41492

American (AMR) AF: 0.0562 AC: 859 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.179 AC: 925 AN: 5176

South Asian (SAS) AF: 0.104 AC: 503 AN: 4824

European-Finnish (FIN) AF: 0.00114 AC: 12 AN: 10572

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00334 AC: 227 AN: 68026

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0159 Hom.: 22

Bravo AF: 0.0906

Asia WGS AF: 0.132 AC: 459 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		1.6
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: rs6789086; hg19: chr3-41359908;