dbSNP rs4964879: ULK1:c.1610-127G>A (chr12-131915764-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_003565.4(ULK1):c.1610-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.152 (AC=201,450) in the gnomAD database across 1,326,766 control chromosomes, including 22,896 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.608. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 5083 hom., cov: 33)

Exomes 𝑓: 0.14 ( 17813 hom. )

Consequence

ULK1
NM_003565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

10 publications found

Variant links:

Genes affected

ULK1 (HGNC:12558): (unc-51 like autophagy activating kinase 1) Enables identical protein binding activity; protein serine/threonine kinase activity; and small GTPase binding activity. Involved in several processes, including autophagosome assembly; positive regulation by symbiont of host autophagy; and protein phosphorylation. Located in autophagosome; cytosol; and phagophore assembly site membrane. Is extrinsic component of autophagosome membrane; extrinsic component of omegasome membrane; and extrinsic component of phagophore assembly site membrane. Part of Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ULK1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003565.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6079 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_003565.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	NM_003565.4	MANE Select	c.1610-127G>A		intron	N/A	NP_003556.2	O75385

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ULK1	ENST00000321867.6	TSL:1 MANE Select	c.1610-127G>A	intron	N/A	ENSP00000324560.3	O75385
ULK1	ENST00000939866.1		c.1679-127G>A	intron	N/A	ENSP00000609925.1	A0ACI8U4T8
ULK1	ENST00000939867.1		c.1607-127G>A	intron	N/A	ENSP00000609926.1	A0ACI8U4Q1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33147

AN:

151946

Hom.:

5085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.143

AC:

168288

AN:

1174702

Hom.:

17813

AF XY:

0.141

AC XY:

83142

AN XY:

589346

show subpopulations

African (AFR)

AF:

0.396

AC:

10305

AN:

26052

American (AMR)

AF:

0.224

AC:

6170

AN:

27534

Ashkenazi Jewish (ASJ)

AF:

0.0799

AC:

1726

AN:

21600

East Asian (EAS)

AF:

0.615

AC:

22579

AN:

36734

South Asian (SAS)

AF:

0.123

AC:

8827

AN:

72034

European-Finnish (FIN)

AF:

0.156

AC:

5555

AN:

35724

Middle Eastern (MID)

AF:

0.0853

AC:

350

AN:

4104

European-Non Finnish (NFE)

AF:

0.117

AC:

104920

AN:

900486

Other (OTH)

AF:

0.156

AC:

7856

AN:

50434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7151

14302

21453

28604

35755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3928

7856

11784

15712

19640

<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:

0.218

AC:

33162

AN:

152064

Hom.:

5083

Cov.:

AF XY:

0.219

AC XY:

16279

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.392

AC:

16242

AN:

41466

American (AMR)

AF:

0.181

AC:

2775

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3470

East Asian (EAS)

AF:

0.580

AC:

2986

AN:

5146

South Asian (SAS)

AF:

0.135

AC:

650

AN:

4824

European-Finnish (FIN)

AF:

0.156

AC:

1656

AN:

10588

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8106

AN:

67962

Other (OTH)

AF:

0.182

AC:

385

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1169

2339

3508

4678

5847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.145

Hom.:

2674

Bravo

AF:

0.231

Asia WGS

AF:

0.332

AC:

1153

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.639

AC:

78382

AN:

122616

Turkish Variome

AF:

0.0996

AC:

154

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.574

AC:

5141

AN:

8960

Hom.:

1483

ABraOM SABE-WGS-1171

AF:

0.174

AC:

407

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.3

(source)

DANN

Benign

0.57

PhyloP100

-0.15

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over