12-131920876-C-T

Variant names:

• chr12-131920876-C-T
• rs7300908
• NM_003565.4:c.2962-224C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.79

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.2962-224C>T		intron_variant	Intron 26 of 27	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.3031-224C>T		intron_variant	Intron 26 of 27		XP_011537100.1
ULK1	XM_011538799.3	c.2944-224C>T		intron_variant	Intron 26 of 27		XP_011537101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.2962-224C>T		intron_variant	Intron 26 of 27	1	NM_003565.4	ENSP00000324560.3
ULK1	ENST00000540568.1	n.810C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
ULK1	ENST00000540647.5	n.831-224C>T		intron_variant	Intron 4 of 5	2
ULK1	ENST00000544718.1	n.897-224C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18068 AN: 152118 Hom.: 2303 Cov.: 33

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.: 6 AF XY: 0.0409 AC XY: 9518 AN XY: 232572

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.0619

Gnomad4 SAS exome AF: 0.0190

Gnomad4 FIN exome AF: 0.00554

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.0639

GnomAD4 genome AF: 0.119 AC: 18120 AN: 152236 Hom.: 2310 Cov.: 33 AF XY: 0.118 AC XY: 8780 AN XY: 74446

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0994

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0308 Hom.: 50

Bravo AF: 0.143

Asia WGS AF: 0.0710 AC: 247 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	0.24
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs7300908; hg19: chr12-132405421;