chr3-41831385-C-T

Variant names:

• chr3-41831385-C-T
• rs9816772
• NM_017886.4:c.1764+4479G>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.1764+4479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 147,638 control chromosomes in the GnomAD database, including 5,479 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 0.24 (5479 hom., cov: 28)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 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.1764+4479G>A		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.1764+4479G>A		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.858+4479G>A		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.1764+4479G>A		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.1761+4479G>A		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.1764+4479G>A		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 35952 AN: 147596 Hom.: 5465 Cov.: 28

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.244 AC: 35977 AN: 147638 Hom.: 5479 Cov.: 28 AF XY: 0.245 AC XY: 17625 AN XY: 71832

African (AFR) AF: 0.436 AC: 17504 AN: 40162

American (AMR) AF: 0.182 AC: 2689 AN: 14744

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3454

East Asian (EAS) AF: 0.164 AC: 836 AN: 5086

South Asian (SAS) AF: 0.177 AC: 833 AN: 4710

European-Finnish (FIN) AF: 0.228 AC: 2044 AN: 8982

Middle Eastern (MID) AF: 0.335 AC: 93 AN: 278

European-Non Finnish (NFE) AF: 0.161 AC: 10825 AN: 67274

Other (OTH) AF: 0.234 AC: 477 AN: 2040

Alfa AF: 0.202 Hom.: 478

Bravo AF: 0.248

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.092
DANN	Benign	0.53
PhyloP100		-0.84
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: rs9816772; hg19: chr3-41872877;