3-41883931-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017886.4(ULK4):c.1599A>G(p.Val533Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,611,248 control chromosomes in the GnomAD database, including 783,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66468 hom., cov: 34)

Exomes 𝑓: 0.99 ( 717000 hom. )

Consequence

ULK4
NM_017886.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.04

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-41883931-T-C is Benign according to our data. Variant chr3-41883931-T-C is described in ClinVar as Benign. ClinVar VariationId is 403585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.04 with no splicing effect.

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 rank	MANE	Protein	UniProt
ULK4	NM_017886.4 link	c.1599A>G	p.Val533Val	synonymous_variant	Exon 17 of 37	ENST00000301831.9	NP_060356.2	Q96C45
ULK4	NM_001322500.2 link	c.1599A>G	p.Val533Val	synonymous_variant	Exon 17 of 36		NP_001309429.1
ULK4	NM_001322501.2 link	c.693A>G	p.Val231Val	synonymous_variant	Exon 16 of 36		NP_001309430.1
ULK4	NR_136342.2 link	n.1665A>G		non_coding_transcript_exon_variant	Exon 16 of 35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9 link	c.1599A>G	p.Val533Val	synonymous_variant	Exon 17 of 37	2	NM_017886.4	ENSP00000301831.4		Q96C45
ULK4	ENST00000420927.5 link	c.1599A>G	p.Val533Val	synonymous_variant	Exon 17 of 18	1		ENSP00000412187.1		A0A0C4DG77

Frequencies

GnomAD3 genomes

AF:

0.929

AC:

141311

AN:

152176

Hom.:

66440

Cov.:

show subpopulations

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:

0.999

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.945

GnomAD2 exomes

AF:

0.980

AC:

244427

AN:

249538

AF XY:

0.984

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.984

GnomAD4 exome

AF:

0.991

AC:

1445208

AN:

1458954

Hom.:

717000

Cov.:

AF XY:

0.992

AC XY:

719841

AN XY:

726012

show subpopulations

African (AFR)

AF:

0.740

AC:

24716

AN:

33390

American (AMR)

AF:

0.980

AC:

43844

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.981

AC:

25604

AN:

26102

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39692

South Asian (SAS)

AF:

0.999

AC:

86075

AN:

86188

European-Finnish (FIN)

AF:

0.999

AC:

53374

AN:

53420

Middle Eastern (MID)

AF:

0.949

AC:

5470

AN:

5766

European-Non Finnish (NFE)

AF:

0.998

AC:

1107417

AN:

1109378

Other (OTH)

AF:

0.979

AC:

59017

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

514

1028

1541

2055

2569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21578

43156

64734

86312

107890

<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:

0.928

AC:

141385

AN:

152294

Hom.:

66468

Cov.:

AF XY:

0.930

AC XY:

69288

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.760

AC:

31547

AN:

41518

American (AMR)

AF:

0.964

AC:

14759

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3400

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5190

AN:

5190

South Asian (SAS)

AF:

0.999

AC:

4819

AN:

4824

European-Finnish (FIN)

AF:

0.999

AC:

10612

AN:

10622

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.997

AC:

67868

AN:

68044

Other (OTH)

AF:

0.946

AC:

1999

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

437

873

1310

1746

2183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.963

Hom.:

42375

Bravo

AF:

0.918

Asia WGS

AF:

0.975

AC:

3390

AN:

3478

EpiCase

AF:

0.995

EpiControl

AF:

0.996

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

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.4

(source)

DANN

Benign

0.61

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over