rs1717003

Variant names:

• chr3-41895508-C-T
• rs1717003
• NM_017886.4:c.1577+10G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_017886.4(ULK4):​c.1577+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,060 control chromosomes in the GnomAD database, including 39,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (39433 hom., cov: 32)
  • Exomes 𝑓: 0.81 (422173 hom.)
  • Failed GnomAD Quality Control
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0970
• Publications: 12 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-41895508-C-T is Benign according to our data. Variant chr3-41895508-C-T is described in ClinVar as Benign. ClinVar VariationId is 403586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.1577+10G>A		intron_variant	Intron 16 of 36	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.1577+10G>A		intron_variant	Intron 16 of 35		NP_001309429.1
ULK4	NM_001322501.2	c.671+10G>A		intron_variant	Intron 15 of 35		NP_001309430.1
ULK4	NR_136342.2	n.1643+10G>A		intron_variant	Intron 15 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1577+10G>A		intron_variant	Intron 16 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000420927.5	c.1577+10G>A		intron_variant	Intron 16 of 17	1		ENSP00000412187.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104670 AN: 151940 Hom.: 39415 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.769 AC: 101864 AN: 132404 AF XY: 0.776

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.832

Gnomad ASJ exome AF: 0.806

Gnomad EAS exome AF: 0.791

Gnomad FIN exome AF: 0.764

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.764

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.815 AC: 1025270 AN: 1258108 Hom.: 422173 Cov.: 18 AF XY: 0.816 AC XY: 510323 AN XY: 625068

African (AFR) AF: 0.316 AC: 8525 AN: 26986

American (AMR) AF: 0.833 AC: 19899 AN: 23880

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 17959 AN: 22234

East Asian (EAS) AF: 0.853 AC: 27981 AN: 32798

South Asian (SAS) AF: 0.809 AC: 51032 AN: 63058

European-Finnish (FIN) AF: 0.782 AC: 37381 AN: 47802

Middle Eastern (MID) AF: 0.644 AC: 2987 AN: 4640

European-Non Finnish (NFE) AF: 0.831 AC: 818687 AN: 984728

Other (OTH) AF: 0.785 AC: 40819 AN: 51982

GnomAD4 genome AF: 0.689 AC: 104705 AN: 152060 Hom.: 39433 Cov.: 32 AF XY: 0.690 AC XY: 51280 AN XY: 74336

African (AFR) AF: 0.353 AC: 14635 AN: 41424

American (AMR) AF: 0.789 AC: 12057 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2804 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4327 AN: 5184

South Asian (SAS) AF: 0.811 AC: 3916 AN: 4826

European-Finnish (FIN) AF: 0.776 AC: 8183 AN: 10548

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56386 AN: 68000

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.725 Hom.: 12656

Bravo AF: 0.675

Asia WGS AF: 0.804 AC: 2784 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		-0.097
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: rs1717003; hg19: chr3-41937000;