rs1625226

chr3-41898501-T-Achr3-41898501-T-Cchr3-41898501-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017886.4(ULK4):c.1288-9A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,348,298 control chromosomes in the GnomAD database, including 604,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (65894 hom., cov: 30)
  • Exomes 𝑓: 0.95 (538376 hom.)
• Consequence: ULK4 NM_017886.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002206
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.694

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-41898501-T-A is Benign according to our data. Variant chr3-41898501-T-A is described in ClinVar as [Benign]. Clinvar id is 403588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK4	NM_017886.4	c.1288-9A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000301831.9
ULK4	NM_001322500.2	c.1288-9A>T		splice_polypyrimidine_tract_variant, intron_variant
ULK4	NM_001322501.2	c.382-9A>T		splice_polypyrimidine_tract_variant, intron_variant
ULK4	NR_136342.2	n.1354-9A>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.1288-9A>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_017886.4	P1
ULK4	ENST00000420927.5	c.1288-9A>T		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 140227 AN: 151144 Hom.: 65867 Cov.: 30

Gnomad AFR AF: 0.760

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.944

GnomAD3 exomes AF: 0.934 AC: 192017 AN: 205578 Hom.: 89653 AF XY: 0.939 AC XY: 104538 AN XY: 111376

Gnomad AFR exome AF: 0.729

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.912

Gnomad EAS exome AF: 0.956

Gnomad SAS exome AF: 0.939

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.928

GnomAD4 exome AF: 0.949 AC: 1135678 AN: 1197038 Hom.: 538376 Cov.: 22 AF XY: 0.949 AC XY: 565285 AN XY: 595600

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 0.926

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.960

Gnomad4 NFE exome AF: 0.958

Gnomad4 OTH exome AF: 0.934

GnomAD4 genome AF: 0.928 AC: 140299 AN: 151260 Hom.: 65894 Cov.: 30 AF XY: 0.929 AC XY: 68711 AN XY: 73930

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.944

Alfa AF: 0.942 Hom.: 12814

Bravo AF: 0.918

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.034
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0040
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: rs1625226; hg19: chr3-41939993;