dbSNP rs9652059: ULK1:c.246+1551T>C (chr12-131897375-T-C) – 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.246+1551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,152 control chromosomes in the GnomAD database, including 34,206 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 0.63 ( 34203 hom., cov: 33)

Exomes 𝑓: 0.80 ( 3 hom. )

Consequence

ULK1
NM_003565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

14 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:

ENSG00000279283 (HGNC:):

ENSG00000279283 links:

Genome browser will be placed here

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 (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4 link	c.246+1551T>C	intron_variant	Intron 3 of 27	ENST00000321867.6	NP_003556.2	O75385
ULK1	XM_011538798.4 link	c.246+1551T>C	intron_variant	Intron 3 of 27		XP_011537100.1
ULK1	XM_011538799.3 link	c.246+1551T>C	intron_variant	Intron 3 of 27		XP_011537101.1
ULK1	XR_007063134.1 link	n.626+1551T>C	intron_variant	Intron 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6 link	c.246+1551T>C		intron_variant	Intron 3 of 27	1	NM_003565.4	ENSP00000324560.3		O75385
ENSG00000279283	ENST00000624048.1 link	n.876T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95650

AN:

152024

Hom.:

34210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.760

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.824

Gnomad OTH

AF:

0.670

GnomAD4 exome

AF:

0.800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.800

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.629

AC:

95655

AN:

152142

Hom.:

34203

Cov.:

AF XY:

0.620

AC XY:

46105

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.292

AC:

12098

AN:

41482

American (AMR)

AF:

0.686

AC:

10496

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.760

AC:

2636

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1635

AN:

5166

South Asian (SAS)

AF:

0.668

AC:

3225

AN:

4828

European-Finnish (FIN)

AF:

0.671

AC:

7100

AN:

10586

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.823

AC:

55994

AN:

67996

Other (OTH)

AF:

0.672

AC:

1421

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1440

2880

4319

5759

7199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.749

Hom.:

116777

Bravo

AF:

0.613

Asia WGS

AF:

0.489

AC:

1702

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.95

(source)

DANN

Benign

0.19

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over