rs33916626

Positions:

• chr3-41453127-C-T

Variant summary

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

The NM_017886.4(ULK4):​c.3492+2370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,148 control chromosomes in the GnomAD database, including 784 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 0.094 (784 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+2370G>A		intron_variant		ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3492+2370G>A		intron_variant		2	NM_017886.4	ENSP00000301831	P1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14328 AN: 152030 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.0858

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

GnomAD4 genome AF: 0.0943 AC: 14352 AN: 152148 Hom.: 784 Cov.: 32 AF XY: 0.0954 AC XY: 7093 AN XY: 74384

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.0901

Alfa AF: 0.0919 Hom.: 697

Bravo AF: 0.0991

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.76

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: rs33916626; hg19: chr3-41494618;