3-41439191-A-G

Variant names:

• chr3-41439191-A-G
• rs2632594
• NM_017886.4:c.3492+16306T>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.3492+16306T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,148 control chromosomes in the GnomAD database, including 59,933 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 0.88 (59933 hom., cov: 30)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+16306T>C		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+16306T>C		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134499 AN: 152030 Hom.: 59867 Cov.: 30

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.885 AC: 134624 AN: 152148 Hom.: 59933 Cov.: 30 AF XY: 0.886 AC XY: 65903 AN XY: 74364

African (AFR) AF: 0.972 AC: 40382 AN: 41532

American (AMR) AF: 0.874 AC: 13351 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2750 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5156 AN: 5160

South Asian (SAS) AF: 0.902 AC: 4346 AN: 4818

European-Finnish (FIN) AF: 0.853 AC: 9027 AN: 10582

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56795 AN: 68000

Other (OTH) AF: 0.856 AC: 1808 AN: 2112

Alfa AF: 0.850 Hom.: 34114

Bravo AF: 0.889

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.31
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: rs2632594; hg19: chr3-41480682;