Genetic Variant NM_003565.4:c.2962-212G>T (chr12-131920888-G-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.2962-212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 642,326 control chromosomes in the GnomAD database, including 2,961 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 0.10 ( 1059 hom., cov: 33)

Exomes 𝑓: 0.078 ( 1902 hom. )

Consequence

ULK1
NM_003565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

5 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

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4 link	c.2962-212G>T	intron_variant	Intron 26 of 27	ENST00000321867.6	NP_003556.2	O75385
ULK1	XM_011538798.4 link	c.3031-212G>T	intron_variant	Intron 26 of 27		XP_011537100.1
ULK1	XM_011538799.3 link	c.2944-212G>T	intron_variant	Intron 26 of 27		XP_011537101.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ULK1	ENST00000321867.6 link	c.2962-212G>T	intron_variant	Intron 26 of 27	1	NM_003565.4	ENSP00000324560.3	O75385
ULK1	ENST00000540568.1 link	n.822G>T	non_coding_transcript_exon_variant	Exon 1 of 2	2
ULK1	ENST00000540647.5 link	n.831-212G>T	intron_variant	Intron 4 of 5	2
ULK1	ENST00000544718.1 link	n.897-212G>T	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15808

AN:

152040

Hom.:

1059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0737

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0851

GnomAD4 exome

AF:

0.0782

AC:

38309

AN:

490168

Hom.:

1902

Cov.:

AF XY:

0.0794

AC XY:

19982

AN XY:

251732

show subpopulations

African (AFR)

AF:

0.166

AC:

2217

AN:

13320

American (AMR)

AF:

0.0689

AC:

1167

AN:

16928

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

1725

AN:

13064

East Asian (EAS)

AF:

0.0871

AC:

2635

AN:

30244

South Asian (SAS)

AF:

0.112

AC:

4153

AN:

36938

European-Finnish (FIN)

AF:

0.168

AC:

4609

AN:

27478

Middle Eastern (MID)

AF:

0.0888

AC:

179

AN:

2016

European-Non Finnish (NFE)

AF:

0.0598

AC:

19340

AN:

323666

Other (OTH)

AF:

0.0861

AC:

2284

AN:

26514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1718

3435

5153

6870

8588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.104

AC:

15825

AN:

152158

Hom.:

1059

Cov.:

AF XY:

0.109

AC XY:

8126

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.164

AC:

6800

AN:

41502

American (AMR)

AF:

0.0679

AC:

1037

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3466

East Asian (EAS)

AF:

0.0734

AC:

380

AN:

5174

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4818

European-Finnish (FIN)

AF:

0.201

AC:

2127

AN:

10586

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0623

AC:

4237

AN:

68010

Other (OTH)

AF:

0.0866

AC:

183

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

686

1372

2059

2745

3431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0293

Hom.:

Bravo

AF:

0.0957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.82

PhyloP100

-0.068

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

Computational scores

Splicing

Publications

Other links and lift over