3-41318417-G-T

Position:

• chr3-41318417-G-T

Variant summary

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

The NM_017886.4(ULK4):​c.3679-68843C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,168 control chromosomes in the GnomAD database, including 1,228 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 0.080 (1228 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3679-68843C>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.3679-68843C>A		intron_variant		2	NM_017886.4	ENSP00000301831	P1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12153 AN: 152050 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0801 AC: 12183 AN: 152168 Hom.: 1228 Cov.: 32 AF XY: 0.0809 AC XY: 6021 AN XY: 74390

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.00114

Gnomad4 NFE AF: 0.00334

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.00364 Hom.: 2

Bravo AF: 0.0906

Asia WGS AF: 0.132 AC: 459 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.72

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: rs6789086; hg19: chr3-41359908;