NM_017886.4:c.670A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I224F) has been classified as Uncertain significance.

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

Publications

56 publications found

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 Gene-Disease associations (from GenCC):

prostate cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ULK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ULK4	NM_017886.4	MANE Select	c.670A>G	p.Ile224Val	missense	Exon 7 of 37	NP_060356.2	Q96C45
ULK4	NM_001322500.2		c.670A>G	p.Ile224Val	missense	Exon 7 of 36	NP_001309429.1
ULK4	NM_001322501.2		c.-161A>G		5_prime_UTR	Exon 7 of 36	NP_001309430.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ULK4	ENST00000301831.9	TSL:2 MANE Select	c.670A>G	p.Ile224Val	missense	Exon 7 of 37	ENSP00000301831.4	Q96C45
ULK4	ENST00000420927.5	TSL:1	c.670A>G	p.Ile224Val	missense	Exon 7 of 18	ENSP00000412187.1	A0A0C4DG77
ULK4	ENST00000951851.1		c.670A>G	p.Ile224Val	missense	Exon 7 of 37	ENSP00000621910.1

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

GnomAD2 exomes

AF:

0.787

AC:

180629

AN:

229482

AF XY:

0.793

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 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

African (AFR)

AF:

0.307

AC:

9908

AN:

32282

American (AMR)

AF:

0.845

AC:

33412

AN:

39556

Ashkenazi Jewish (ASJ)

AF:

0.809

AC:

20758

AN:

25658

East Asian (EAS)

AF:

0.852

AC:

33120

AN:

38864

South Asian (SAS)

AF:

0.821

AC:

63963

AN:

77932

European-Finnish (FIN)

AF:

0.786

AC:

41777

AN:

53154

Middle Eastern (MID)

AF:

0.649

AC:

3676

AN:

5660

European-Non Finnish (NFE)

AF:

0.832

AC:

913156

AN:

1097754

Other (OTH)

AF:

0.787

AC:

46635

AN:

59252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

8716

17432

26147

34863

43579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20704

41408

62112

82816

103520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.680

AC:

103031

AN:

151556

Hom.:

38612

Cov.:

AF XY:

0.681

AC XY:

50409

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.332

AC:

13703

AN:

41238

American (AMR)

AF:

0.778

AC:

11841

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

2790

AN:

3472

East Asian (EAS)

AF:

0.832

AC:

4292

AN:

5158

South Asian (SAS)

AF:

0.821

AC:

3951

AN:

4814

European-Finnish (FIN)

AF:

0.775

AC:

8026

AN:

10358

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.825

AC:

56058

AN:

67984

Other (OTH)

AF:

0.699

AC:

1473

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1314

2628

3942

5256

6570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.788

Hom.:

191955

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.39

MetaRNN

Benign

6.1e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PhyloP100

0.14

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.41

REVEL

Benign

0.048

Sift

Benign

0.54

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.015

MPC

0.032

ClinPred

0.0018

GERP RS

-5.9

Varity_R

0.064

gMVP

0.14

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over