3-41946428-T-C

Variant names:

• chr3-41946428-T-C
• rs1717027
• NM_017886.4:c.138+8194A>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.138+8194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,092 control chromosomes in the GnomAD database, including 39,197 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 0.68 (39197 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 20 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 (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.138+8194A>G		intron_variant	Intron 2 of 36	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.138+8194A>G		intron_variant	Intron 2 of 35		NP_001309429.1
ULK4	NM_001322501.2	c.-693+8194A>G		intron_variant	Intron 2 of 35		NP_001309430.1
ULK4	NR_136342.2	n.274+8194A>G		intron_variant	Intron 2 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.138+8194A>G		intron_variant	Intron 2 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104116 AN: 151974 Hom.: 39178 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.685 AC: 104151 AN: 152092 Hom.: 39197 Cov.: 31 AF XY: 0.686 AC XY: 51031 AN XY: 74352

African (AFR) AF: 0.342 AC: 14194 AN: 41452

American (AMR) AF: 0.783 AC: 11966 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2807 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4318 AN: 5178

South Asian (SAS) AF: 0.821 AC: 3951 AN: 4812

European-Finnish (FIN) AF: 0.775 AC: 8210 AN: 10592

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56331 AN: 68002

Other (OTH) AF: 0.706 AC: 1488 AN: 2108

Alfa AF: 0.761 Hom.: 72044

Bravo AF: 0.671

Asia WGS AF: 0.805 AC: 2799 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	2.7
DANN	Benign	0.74
PhyloP100		-1.2
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: rs1717027; hg19: chr3-41987920;