3-41453114-T-C

Variant names:

• chr3-41453114-T-C
• rs6809441
• NM_017886.4:c.3492+2383A>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.3492+2383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,020 control chromosomes in the GnomAD database, including 7,749 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 0.31 (7749 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+2383A>G		intron_variant	Intron 34 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3492+2383A>G		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47813 AN: 151902 Hom.: 7739 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.315 AC: 47830 AN: 152020 Hom.: 7749 Cov.: 31 AF XY: 0.308 AC XY: 22924 AN XY: 74314

African (AFR) AF: 0.366 AC: 15185 AN: 41448

American (AMR) AF: 0.227 AC: 3470 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3468

East Asian (EAS) AF: 0.129 AC: 666 AN: 5152

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3076 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21662 AN: 67966

Other (OTH) AF: 0.318 AC: 671 AN: 2110

Alfa AF: 0.313 Hom.: 32551

Bravo AF: 0.310

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.45
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: rs6809441; hg19: chr3-41494605;