3-41460246-A-G

Variant names:

• chr3-41460246-A-G
• rs11129908
• NM_017886.4:c.3393+2841T>C

Variant summary

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

The NM_017886.4(ULK4):​c.3393+2841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,914 control chromosomes in the GnomAD database, including 21,775 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 0.53 (21775 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 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.3393+2841T>C		intron	N/A	NP_060356.2
	ULK4	NM_001322500.2		c.3393+2841T>C		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2487+2841T>C		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.3393+2841T>C		intron	N/A	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80907 AN: 151796 Hom.: 21757 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.533 AC: 80958 AN: 151914 Hom.: 21775 Cov.: 31 AF XY: 0.533 AC XY: 39527 AN XY: 74210

African (AFR) AF: 0.610 AC: 25284 AN: 41424

American (AMR) AF: 0.462 AC: 7053 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3466

East Asian (EAS) AF: 0.667 AC: 3436 AN: 5150

South Asian (SAS) AF: 0.604 AC: 2909 AN: 4818

European-Finnish (FIN) AF: 0.502 AC: 5291 AN: 10542

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33562 AN: 67932

Other (OTH) AF: 0.522 AC: 1099 AN: 2106

Alfa AF: 0.511 Hom.: 3748

Bravo AF: 0.533

Asia WGS AF: 0.619 AC: 2152 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.78
PhyloP100		-0.52
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: rs11129908; hg19: chr3-41501737;