rs1717003

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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

GnomAD3 exomes AF: 0.769 AC: 101864 AN: 132404 Hom.: 40349 AF XY: 0.776 AC XY: 56396 AN XY: 72702

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 SAS exome AF: 0.805

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

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.853

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.785

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.711

Alfa AF: 0.731 Hom.: 12601

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.4
DANN	Benign	0.83

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: rs1717003; hg19: chr3-41937000;