chr3-41485476-A-G

Variant names:

• chr3-41485476-A-G
• rs9878069
• NM_017886.4:c.3227-22223T>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.3227-22223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,130 control chromosomes in the GnomAD database, including 7,533 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 0.31 (7533 hom., cov: 33)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3227-22223T>C		intron_variant	Intron 32 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3227-22223T>C		intron_variant	Intron 32 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47170 AN: 152010 Hom.: 7532 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.310 AC: 47172 AN: 152130 Hom.: 7533 Cov.: 33 AF XY: 0.302 AC XY: 22463 AN XY: 74372

African (AFR) AF: 0.315 AC: 13051 AN: 41480

American (AMR) AF: 0.246 AC: 3758 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5188

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4816

European-Finnish (FIN) AF: 0.265 AC: 2806 AN: 10598

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22961 AN: 67972

Other (OTH) AF: 0.334 AC: 706 AN: 2116

Alfa AF: 0.287 Hom.: 2544

Bravo AF: 0.307

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		0.30
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: rs9878069; hg19: chr3-41526967;