chr3-41452100-T-A

Variant names:

• chr3-41452100-T-A
• rs7649806
• NM_017886.4:c.3492+3397A>T

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+3397A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,006 control chromosomes in the GnomAD database, including 22,686 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 0.52 (22686 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+3397A>T		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+3397A>T		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79194 AN: 151888 Hom.: 22647 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.522 AC: 79279 AN: 152006 Hom.: 22686 Cov.: 31 AF XY: 0.522 AC XY: 38752 AN XY: 74288

African (AFR) AF: 0.770 AC: 31911 AN: 41446

American (AMR) AF: 0.422 AC: 6439 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3543 AN: 5174

South Asian (SAS) AF: 0.542 AC: 2609 AN: 4814

European-Finnish (FIN) AF: 0.426 AC: 4501 AN: 10568

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.400 AC: 27152 AN: 67952

Other (OTH) AF: 0.510 AC: 1074 AN: 2104

Alfa AF: 0.455 Hom.: 2016

Bravo AF: 0.533

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		-0.027
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: rs7649806; hg19: chr3-41493591;