3-41871159-G-A

Variant names:

• chr3-41871159-G-A
• rs9815354
• NM_017886.4:c.1656+12715C>T

Variant summary

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

The NM_017886.4(ULK4):​c.1656+12715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,012 control chromosomes in the GnomAD database, including 2,525 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 0.18 (2525 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 67 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.1656+12715C>T		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.1656+12715C>T		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.750+12715C>T		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.1656+12715C>T		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000951851.1		c.1653+12715C>T		intron	N/A	ENSP00000621910.1
	ULK4	ENST00000889811.1		c.1656+12715C>T		intron	N/A	ENSP00000559870.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27300 AN: 151894 Hom.: 2521 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.180 AC: 27309 AN: 152012 Hom.: 2525 Cov.: 32 AF XY: 0.182 AC XY: 13546 AN XY: 74290

African (AFR) AF: 0.196 AC: 8118 AN: 41466

American (AMR) AF: 0.156 AC: 2379 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3468

East Asian (EAS) AF: 0.166 AC: 858 AN: 5164

South Asian (SAS) AF: 0.186 AC: 895 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2374 AN: 10546

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11396 AN: 67968

Other (OTH) AF: 0.193 AC: 405 AN: 2102

Alfa AF: 0.156 Hom.: 3572

Bravo AF: 0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.16
PhyloP100		0.17
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: rs9815354; hg19: chr3-41912651;