chr3-41939998-C-A

Variant names:

• chr3-41939998-C-A
• rs1717020
• NM_017886.4:c.139-1801G>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.139-1801G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,652 control chromosomes in the GnomAD database, including 39,522 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 0.69 (39522 hom., cov: 29)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 13 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.139-1801G>T		intron_variant	Intron 2 of 36	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.139-1801G>T		intron_variant	Intron 2 of 35		NP_001309429.1
ULK4	NM_001322501.2	c.-692-1801G>T		intron_variant	Intron 2 of 35		NP_001309430.1
ULK4	NR_136342.2	n.275-1801G>T		intron_variant	Intron 2 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.139-1801G>T		intron_variant	Intron 2 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.693 AC: 104980 AN: 151536 Hom.: 39501 Cov.: 29

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.693 AC: 105023 AN: 151652 Hom.: 39522 Cov.: 29 AF XY: 0.694 AC XY: 51422 AN XY: 74104

African (AFR) AF: 0.369 AC: 15244 AN: 41316

American (AMR) AF: 0.787 AC: 11998 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2805 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4293 AN: 5154

South Asian (SAS) AF: 0.820 AC: 3943 AN: 4806

European-Finnish (FIN) AF: 0.775 AC: 8084 AN: 10434

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56269 AN: 67912

Other (OTH) AF: 0.710 AC: 1495 AN: 2106

Alfa AF: 0.713 Hom.: 4860

Bravo AF: 0.680

Asia WGS AF: 0.808 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.099
DANN	Benign	0.52
PhyloP100		-2.2
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: rs1717020; hg19: chr3-41981490;