rs2128834

Positions:

• chr3-41821153-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017886.4(ULK4):​c.1765-1647T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,012 control chromosomes in the GnomAD database, including 6,119 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 0.25 (6119 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK4	NM_017886.4	c.1765-1647T>C		intron_variant		ENST00000301831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.1765-1647T>C		intron_variant		2	NM_017886.4	P1
ULK4	ENST00000460406.1	n.246-1647T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38695 AN: 151894 Hom.: 6097 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.255 AC: 38748 AN: 152012 Hom.: 6119 Cov.: 32 AF XY: 0.255 AC XY: 18974 AN XY: 74298

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.252

Alfa AF: 0.208 Hom.: 681

Bravo AF: 0.261

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs2128834; hg19: chr3-41862645;