dbSNP rs1717003: ULK4:c.1577+10G>A (chr3-41895508-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_017886.4(ULK4):c.1577+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,060 control chromosomes in the GnomAD database, including 39,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 39433 hom., cov: 32)

Exomes 𝑓: 0.81 ( 422173 hom. )

Failed GnomAD Quality Control

Consequence

ULK4
NM_017886.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0970

Publications

12 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-41895508-C-T is Benign according to our data. Variant chr3-41895508-C-T is described in ClinVar as Benign. ClinVar VariationId is 403586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 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	Effect	Exon Rank	Protein	UniProt
ULK4	NM_017886.4	MANE Select	c.1577+10G>A	intron	N/A	NP_060356.2	Q96C45
ULK4	NM_001322500.2		c.1577+10G>A	intron	N/A	NP_001309429.1
ULK4	NM_001322501.2		c.671+10G>A	intron	N/A	NP_001309430.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ULK4	ENST00000301831.9	TSL:2 MANE Select	c.1577+10G>A	intron	N/A	ENSP00000301831.4	Q96C45
ULK4	ENST00000420927.5	TSL:1	c.1577+10G>A	intron	N/A	ENSP00000412187.1	A0A0C4DG77
ULK4	ENST00000951851.1		c.1574+10G>A	intron	N/A	ENSP00000621910.1

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104670

AN:

151940

Hom.:

39415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.808

Gnomad EAS

AF:

0.834

Gnomad SAS

AF:

0.811

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.709

GnomAD2 exomes

AF:

0.769

AC:

101864

AN:

132404

AF XY:

0.776

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.832

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.791

Gnomad FIN exome

AF:

0.764

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.764

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.815

AC:

1025270

AN:

1258108

Hom.:

422173

Cov.:

AF XY:

0.816

AC XY:

510323

AN XY:

625068

show subpopulations

African (AFR)

AF:

0.316

AC:

8525

AN:

26986

American (AMR)

AF:

0.833

AC:

19899

AN:

23880

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

17959

AN:

22234

East Asian (EAS)

AF:

0.853

AC:

27981

AN:

32798

South Asian (SAS)

AF:

0.809

AC:

51032

AN:

63058

European-Finnish (FIN)

AF:

0.782

AC:

37381

AN:

47802

Middle Eastern (MID)

AF:

0.644

AC:

2987

AN:

4640

European-Non Finnish (NFE)

AF:

0.831

AC:

818687

AN:

984728

Other (OTH)

AF:

0.785

AC:

40819

AN:

51982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

6969

13938

20906

27875

34844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18646

37292

55938

74584

93230

<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:

0.689

AC:

104705

AN:

152060

Hom.:

39433

Cov.:

AF XY:

0.690

AC XY:

51280

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.353

AC:

14635

AN:

41424

American (AMR)

AF:

0.789

AC:

12057

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

2804

AN:

3470

East Asian (EAS)

AF:

0.835

AC:

4327

AN:

5184

South Asian (SAS)

AF:

0.811

AC:

3916

AN:

4826

European-Finnish (FIN)

AF:

0.776

AC:

8183

AN:

10548

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.829

AC:

56386

AN:

68000

Other (OTH)

AF:

0.711

AC:

1502

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1354

2708

4062

5416

6770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.725

Hom.:

12656

Bravo

AF:

0.675

Asia WGS

AF:

0.804

AC:

2784

AN:

3460

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

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.4

(source)

DANN

Benign

0.83

PhyloP100

-0.097

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over