NM_017886.4:c.1848+942G>A

Variant names:

• chr3-41818481-C-T
• rs900569
• NM_017886.4:c.1848+942G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017886.4(ULK4):​c.1848+942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,162 control chromosomes in the GnomAD database, including 31,932 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 0.62 (31932 hom., cov: 33)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 publications found

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]

ULK4 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.1848+942G>A		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.1848+942G>A		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.942+942G>A		intron	N/A	NP_001309430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.1848+942G>A		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.1845+942G>A		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.1764+17383G>A		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94445 AN: 152044 Hom.: 31864 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.621 AC: 94568 AN: 152162 Hom.: 31932 Cov.: 33 AF XY: 0.618 AC XY: 45985 AN XY: 74392

African (AFR) AF: 0.900 AC: 37382 AN: 41554

American (AMR) AF: 0.648 AC: 9902 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2100 AN: 5166

South Asian (SAS) AF: 0.608 AC: 2933 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4890 AN: 10566

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33409 AN: 67982

Other (OTH) AF: 0.604 AC: 1271 AN: 2104

Alfa AF: 0.545 Hom.: 78323

Bravo AF: 0.648

Asia WGS AF: 0.533 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0060
DANN	Benign	0.41
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs900569; hg19: chr3-41859973;