rs7648578

Variant names:

• chr3-41817239-C-T
• rs7648578
• NM_017886.4:c.1848+2184G>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.1848+2184G>A 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 152,052 control chromosomes in the GnomAD database, including 11,167 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 (11167 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 11 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=-0.97).
• 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.1848+2184G>A		intron_variant	Intron 19 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1848+2184G>A		intron_variant	Intron 19 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000460406.1	n.329+2184G>A		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47933 AN: 151934 Hom.: 11124 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.171

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: 48017 AN: 152052 Hom.: 11167 Cov.: 32 AF XY: 0.315 AC XY: 23384 AN XY: 74316

African (AFR) AF: 0.661 AC: 27386 AN: 41456

American (AMR) AF: 0.214 AC: 3267 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.165 AC: 853 AN: 5160

South Asian (SAS) AF: 0.188 AC: 909 AN: 4830

European-Finnish (FIN) AF: 0.225 AC: 2379 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11631 AN: 67980

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.253 Hom.: 1290

Bravo AF: 0.329

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.65
PhyloP100		-0.74
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: rs7648578; hg19: chr3-41858731;