3-41452940-C-T

Position:

• chr3-41452940-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+2557G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,862 control chromosomes in the GnomAD database, including 26,359 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 0.57 (26359 hom., cov: 31)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3492+2557G>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+2557G>A		intron_variant		2	NM_017886.4	ENSP00000301831	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86770 AN: 151744 Hom.: 26310 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.572 AC: 86860 AN: 151862 Hom.: 26359 Cov.: 31 AF XY: 0.571 AC XY: 42382 AN XY: 74198

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.554

Alfa AF: 0.512 Hom.: 3507

Bravo AF: 0.579

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.80

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: rs6794510; hg19: chr3-41494431;