3-41405135-T-C

Variant names:

• chr3-41405135-T-C
• rs9311275
• NM_017886.4:c.3493-6871A>G

Variant summary

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

The NM_017886.4(ULK4):​c.3493-6871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,730 control chromosomes in the GnomAD database, including 26,601 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 (26601 hom., cov: 30)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3493-6871A>G		intron_variant	Intron 34 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3493-6871A>G		intron_variant	Intron 34 of 36	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87126 AN: 151610 Hom.: 26559 Cov.: 30

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.575 AC: 87206 AN: 151730 Hom.: 26601 Cov.: 30 AF XY: 0.572 AC XY: 42422 AN XY: 74124

African (AFR) AF: 0.808 AC: 33426 AN: 41384

American (AMR) AF: 0.479 AC: 7300 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1690 AN: 3464

East Asian (EAS) AF: 0.511 AC: 2621 AN: 5126

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4808

European-Finnish (FIN) AF: 0.498 AC: 5237 AN: 10518

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32376 AN: 67882

Other (OTH) AF: 0.561 AC: 1181 AN: 2106

Alfa AF: 0.394 Hom.: 1224

Bravo AF: 0.584

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.98
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: rs9311275; hg19: chr3-41446626;