3-41461821-A-G

Variant names:

• chr3-41461821-A-G
• rs1495704
• NM_017886.4:c.3393+1266T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017886.4(ULK4):​c.3393+1266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,984 control chromosomes in the GnomAD database, including 21,472 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 0.53 (21472 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3393+1266T>C		intron_variant	Intron 33 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3393+1266T>C		intron_variant	Intron 33 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80572 AN: 151868 Hom.: 21460 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.530 AC: 80617 AN: 151984 Hom.: 21472 Cov.: 32 AF XY: 0.530 AC XY: 39386 AN XY: 74278

African (AFR) AF: 0.588 AC: 24368 AN: 41452

American (AMR) AF: 0.464 AC: 7080 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3468

East Asian (EAS) AF: 0.668 AC: 3447 AN: 5164

South Asian (SAS) AF: 0.606 AC: 2928 AN: 4828

European-Finnish (FIN) AF: 0.502 AC: 5289 AN: 10538

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34038 AN: 67960

Other (OTH) AF: 0.519 AC: 1098 AN: 2114

Alfa AF: 0.520 Hom.: 2727

Bravo AF: 0.530

Asia WGS AF: 0.619 AC: 2143 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.79
DANN	Benign	0.60
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: rs1495704; hg19: chr3-41503312;