rs2272007

chr3-41954644-T-Cchr3-41954644-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.116A>G(p.Lys39Arg) variant causes a missense change. The variant allele was found at a frequency of 0.806 in 1,613,112 control chromosomes in the GnomAD database, including 533,999 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (39046 hom., cov: 31)
  • Exomes 𝑓: 0.82 (494953 hom.)
• Consequence: ULK4 NM_017886.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.83

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 (MetaRNN=1.5337359E-6).
• BP6: Variant 3-41954644-T-C is Benign according to our data. Variant chr3-41954644-T-C is described in ClinVar as [Benign]. Clinvar id is 403591.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
ULK4	NM_017886.4	c.116A>G	p.Lys39Arg	missense_variant	2/37	ENST00000301831.9
ULK4	NM_001322500.2	c.116A>G	p.Lys39Arg	missense_variant	2/36
ULK4	NM_001322501.2	c.-715A>G		5_prime_UTR_variant	2/36
ULK4	NR_136342.2	n.252A>G		non_coding_transcript_exon_variant	2/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.116A>G	p.Lys39Arg	missense_variant	2/37	2	NM_017886.4	P1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103699 AN: 151942 Hom.: 39029 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.700

GnomAD3 exomes AF: 0.794 AC: 197721 AN: 249110 Hom.: 80526 AF XY: 0.799 AC XY: 108051 AN XY: 135174

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.818

Gnomad SAS exome AF: 0.825

Gnomad FIN exome AF: 0.777

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.819 AC: 1196390 AN: 1461052 Hom.: 494953 Cov.: 48 AF XY: 0.820 AC XY: 596273 AN XY: 726880

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.852

Gnomad4 ASJ exome AF: 0.812

Gnomad4 EAS exome AF: 0.853

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.682 AC: 103732 AN: 152060 Hom.: 39046 Cov.: 31 AF XY: 0.684 AC XY: 50808 AN XY: 74306

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.702

Alfa AF: 0.799 Hom.: 124106

Bravo AF: 0.668

TwinsUK AF: 0.831 AC: 3083

ALSPAC AF: 0.839 AC: 3234

ESP6500AA AF: 0.358 AC: 1352

ESP6500EA AF: 0.825 AC: 6790

ExAC AF: 0.786 AC: 94999

Asia WGS AF: 0.805 AC: 2801 AN: 3478

EpiCase AF: 0.810

EpiControl AF: 0.813

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
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Benign	0.90
DEOGEN2	Benign	0.0021	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.0000015	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.030	N;.;.
MutationTaster	Benign	0.042	P;P;P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.066
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.20	B;.;.
Vest4		0.087
MPC		0.053
ClinPred		0.015	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.38

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: rs2272007; hg19: chr3-41996136; COSMIC: COSV57209557; COSMIC: COSV57209557;