chr3-41448113-A-C

Position:

• chr3-41448113-A-C

Variant summary

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

The NM_017886.4(ULK4):​c.3492+7384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,076 control chromosomes in the GnomAD database, including 8,164 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 (8164 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+7384T>G		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+7384T>G		intron_variant		2	NM_017886.4	ENSP00000301831	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48931 AN: 151958 Hom.: 8153 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.322 AC: 48954 AN: 152076 Hom.: 8164 Cov.: 32 AF XY: 0.316 AC XY: 23504 AN XY: 74348

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.322

Alfa AF: 0.313 Hom.: 16306

Bravo AF: 0.317

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.77

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: rs6599155; hg19: chr3-41489604;