3-41918514-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017886.4(ULK4):c.670A>G(p.Ile224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,581,668 control chromosomes in the GnomAD database, including 519,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 38612 hom., cov: 30)

Exomes 𝑓: 0.82 ( 480896 hom. )

Consequence

ULK4
NM_017886.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.135

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.0694714E-7).

BP6

Variant 3-41918514-T-C is Benign according to our data. Variant chr3-41918514-T-C is described in ClinVar as [Benign]. Clinvar id is 403590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4 link	c.670A>G	p.Ile224Val	missense_variant	Exon 7 of 37	ENST00000301831.9	NP_060356.2	Q96C45
ULK4	NM_001322500.2 link	c.670A>G	p.Ile224Val	missense_variant	Exon 7 of 36		NP_001309429.1
ULK4	NM_001322501.2 link	c.-161A>G		5_prime_UTR_variant	Exon 7 of 36		NP_001309430.1
ULK4	NR_136342.2 link	n.806A>G		non_coding_transcript_exon_variant	Exon 7 of 35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9 link	c.670A>G	p.Ile224Val	missense_variant	Exon 7 of 37	2	NM_017886.4	ENSP00000301831.4		Q96C45
ULK4	ENST00000420927.5 link	c.670A>G	p.Ile224Val	missense_variant	Exon 7 of 18	1		ENSP00000412187.1		A0A0C4DG77

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

102996

AN:

151440

Hom.:

38593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.804

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.825

Gnomad OTH

AF:

0.697

GnomAD3 exomes

AF:

0.787

AC:

180629

AN:

229482

Hom.:

73091

AF XY:

0.793

AC XY:

98796

AN XY:

124516

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.851

Gnomad ASJ exome

AF:

0.813

Gnomad EAS exome

AF:

0.814

Gnomad SAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.776

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.790

GnomAD4 exome

AF:

0.816

AC:

1166405

AN:

1430112

Hom.:

480896

Cov.:

AF XY:

0.817

AC XY:

580337

AN XY:

710256

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.845

Gnomad4 ASJ exome

AF:

0.809

Gnomad4 EAS exome

AF:

0.852

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.786

Gnomad4 NFE exome

AF:

0.832

Gnomad4 OTH exome

AF:

0.787

GnomAD4 genome

AF:

0.680

AC:

103031

AN:

151556

Hom.:

38612

Cov.:

AF XY:

0.681

AC XY:

50409

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.778

Gnomad4 ASJ

AF:

0.804

Gnomad4 EAS

AF:

0.832

Gnomad4 SAS

AF:

0.821

Gnomad4 FIN

AF:

0.775

Gnomad4 NFE

AF:

0.825

Gnomad4 OTH

AF:

0.699

Alfa

AF:

0.798

Hom.:

109299

Bravo

AF:

0.665

TwinsUK

AF:

0.827

AC:

3066

ALSPAC

AF:

0.835

AC:

3219

ESP6500AA

AF:

0.344

AC:

1249

ESP6500EA

AF:

0.822

AC:

6702

ExAC

AF:

0.785

AC:

94736

Asia WGS

AF:

0.805

AC:

2802

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

DANN

Benign

0.36

DEOGEN2

Benign

0.0013

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

6.1e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.048

Sift

Benign

0.54

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;.

Vest4

0.015

MPC

0.032

ClinPred

0.0018

GERP RS

-5.9

Varity_R

0.064

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over