chr3-41744517-T-C

Variant names:

• chr3-41744517-T-C
• rs6599175
• NM_017886.4:c.2321+9844A>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.2321+9844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,652 control chromosomes in the GnomAD database, including 11,324 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 0.32 (11324 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 28 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.2321+9844A>G		intron_variant	Intron 22 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.2321+9844A>G		intron_variant	Intron 22 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47805 AN: 151534 Hom.: 11283 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.316 AC: 47886 AN: 151652 Hom.: 11324 Cov.: 32 AF XY: 0.315 AC XY: 23330 AN XY: 74110

African (AFR) AF: 0.661 AC: 27159 AN: 41112

American (AMR) AF: 0.204 AC: 3115 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.168 AC: 871 AN: 5182

South Asian (SAS) AF: 0.187 AC: 903 AN: 4820

European-Finnish (FIN) AF: 0.231 AC: 2438 AN: 10534

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11774 AN: 67946

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.223 Hom.: 17432

Bravo AF: 0.330

Asia WGS AF: 0.200 AC: 693 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-2.0
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: rs6599175; hg19: chr3-41786009;