3-41490873-A-C

Variant names:

• chr3-41490873-A-C
• rs1495696
• NM_017886.4:c.3227-27620T>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.3227-27620T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,982 control chromosomes in the GnomAD database, including 12,993 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 (12993 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3227-27620T>G		intron_variant	Intron 32 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3227-27620T>G		intron_variant	Intron 32 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62387 AN: 151866 Hom.: 12989 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.411 AC: 62409 AN: 151982 Hom.: 12993 Cov.: 32 AF XY: 0.404 AC XY: 30012 AN XY: 74312

African (AFR) AF: 0.437 AC: 18087 AN: 41410

American (AMR) AF: 0.388 AC: 5923 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1497 AN: 3468

East Asian (EAS) AF: 0.163 AC: 843 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1884 AN: 4812

European-Finnish (FIN) AF: 0.385 AC: 4072 AN: 10568

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28719 AN: 67962

Other (OTH) AF: 0.421 AC: 890 AN: 2114

Alfa AF: 0.367 Hom.: 3697

Bravo AF: 0.410

Asia WGS AF: 0.317 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.39
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: rs1495696; hg19: chr3-41532364;