3-41489285-T-C

Variant names:

• chr3-41489285-T-C
• rs9311278
• NM_017886.4:c.3227-26032A>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.3227-26032A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,046 control chromosomes in the GnomAD database, including 12,935 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 0.41 (12935 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.3227-26032A>G		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.3227-26032A>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.2321-26032A>G		intron	N/A	NP_001309430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.3227-26032A>G		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.3224-26032A>G		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.3143-26032A>G		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62245 AN: 151928 Hom.: 12931 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.410 AC: 62268 AN: 152046 Hom.: 12935 Cov.: 32 AF XY: 0.403 AC XY: 29927 AN XY: 74338

African (AFR) AF: 0.433 AC: 17958 AN: 41434

American (AMR) AF: 0.387 AC: 5915 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3472

East Asian (EAS) AF: 0.163 AC: 846 AN: 5184

South Asian (SAS) AF: 0.392 AC: 1885 AN: 4812

European-Finnish (FIN) AF: 0.386 AC: 4081 AN: 10568

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.422 AC: 28713 AN: 67994

Other (OTH) AF: 0.419 AC: 881 AN: 2102

Alfa AF: 0.275 Hom.: 691

Bravo AF: 0.409

Asia WGS AF: 0.316 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.78
PhyloP100		-0.34
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: rs9311278; hg19: chr3-41530776;