rs7618902

Positions:

• chr3-41465961-C-G
• chr3-41465961-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.3227-2708G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,916 control chromosomes in the GnomAD database, including 9,181 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 0.33 (9181 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK4	NM_017886.4	c.3227-2708G>C		intron_variant		ENST00000301831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.3227-2708G>C		intron_variant		2	NM_017886.4	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49359 AN: 151796 Hom.: 9156 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.325 AC: 49415 AN: 151916 Hom.: 9181 Cov.: 32 AF XY: 0.320 AC XY: 23761 AN XY: 74226

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.312

Alfa AF: 0.154 Hom.: 270

Bravo AF: 0.325

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.51

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: rs7618902; hg19: chr3-41507452;