NM_017886.4:c.3492+2370G>A

Variant names:

• chr3-41453127-C-T
• rs33916626
• NM_017886.4:c.3492+2370G>A

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+2370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,148 control chromosomes in the GnomAD database, including 784 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 0.094 (784 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+2370G>A		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+2370G>A		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14328 AN: 152030 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.0858

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

GnomAD4 genome AF: 0.0943 AC: 14352 AN: 152148 Hom.: 784 Cov.: 32 AF XY: 0.0954 AC XY: 7093 AN XY: 74384

African (AFR) AF: 0.0948 AC: 3935 AN: 41506

American (AMR) AF: 0.145 AC: 2218 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.0292 AC: 151 AN: 5174

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1163 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0893 AC: 6071 AN: 67992

Other (OTH) AF: 0.0901 AC: 190 AN: 2108

Alfa AF: 0.0938 Hom.: 934

Bravo AF: 0.0991

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.39
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: rs33916626; hg19: chr3-41494618;