Genetic Variant ULK1:c.2962-224C>T (chr12-131920876-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003565.4(ULK1):c.2962-224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 602,810 control chromosomes in the GnomAD database, including 3,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 2310 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1137 hom. )

Consequence

ULK1
NM_003565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.79

Publications

4 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	NM_003565.4	MANE Select	c.2962-224C>T		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.2962-224C>T	intron	N/A	ENSP00000324560.3	O75385
ULK1	ENST00000939866.1		c.3031-224C>T	intron	N/A	ENSP00000609925.1
ULK1	ENST00000939867.1		c.2959-224C>T	intron	N/A	ENSP00000609926.1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18068

AN:

152118

Hom.:

2303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.0994

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.0428

AC:

19272

AN:

450574

Hom.:

1137

Cov.:

AF XY:

0.0409

AC XY:

9518

AN XY:

232572

show subpopulations

African (AFR)

AF:

0.309

AC:

3874

AN:

12542

American (AMR)

AF:

0.156

AC:

2585

AN:

16530

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

372

AN:

12770

East Asian (EAS)

AF:

0.0619

AC:

1845

AN:

29804

South Asian (SAS)

AF:

0.0190

AC:

668

AN:

35152

European-Finnish (FIN)

AF:

0.00554

AC:

151

AN:

27240

Middle Eastern (MID)

AF:

0.0663

AC:

127

AN:

1916

European-Non Finnish (NFE)

AF:

0.0278

AC:

8039

AN:

289426

Other (OTH)

AF:

0.0639

AC:

1611

AN:

25194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

794

1589

2383

3178

3972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.119

AC:

18120

AN:

152236

Hom.:

2310

Cov.:

AF XY:

0.118

AC XY:

8780

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.309

AC:

12827

AN:

41502

American (AMR)

AF:

0.149

AC:

2283

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3470

East Asian (EAS)

AF:

0.0994

AC:

515

AN:

5180

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4822

European-Finnish (FIN)

AF:

0.00348

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0274

AC:

1866

AN:

68028

Other (OTH)

AF:

0.118

AC:

249

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

698

1396

2095

2793

3491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0308

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.74

PhyloP100

-3.8

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