rs6768438

Variant names:

• chr3-41823863-G-A
• rs6768438
• NM_017886.4:c.1765-4357C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-41823863-G-A
• chr3-41823863-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000301831.9(ULK4):​c.1765-4357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,944 control chromosomes in the GnomAD database, including 10,926 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 (10926 hom., cov: 32)
• Consequence: ULK4 ENST00000301831.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000301831.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.1765-4357C>T		intron	N/A	NP_060356.2
	ULK4	NM_001322500.2		c.1765-4357C>T		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.859-4357C>T		intron	N/A	NP_001309430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.1765-4357C>T		intron	N/A	ENSP00000301831.4
	ULK4	ENST00000460406.1	TSL:2	n.246-4357C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47499 AN: 151826 Hom.: 10883 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.313 AC: 47583 AN: 151944 Hom.: 10926 Cov.: 32 AF XY: 0.312 AC XY: 23168 AN XY: 74266

African (AFR) AF: 0.652 AC: 27001 AN: 41402

American (AMR) AF: 0.212 AC: 3238 AN: 15262

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

East Asian (EAS) AF: 0.166 AC: 856 AN: 5162

South Asian (SAS) AF: 0.188 AC: 905 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2389 AN: 10562

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

European-Non Finnish (NFE) AF: 0.171 AC: 11613 AN: 67964

Other (OTH) AF: 0.289 AC: 607 AN: 2102

Alfa AF: 0.249 Hom.: 883

Bravo AF: 0.326

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.74
PhyloP100		-0.50
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: rs6768438; hg19: chr3-41865355;