rs7953348

Positions:

• chr12-131900286-C-T

Variant summary

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

The NM_003565.4(ULK1):​c.246+4462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,114 control chromosomes in the GnomAD database, including 34,552 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 0.64 (34552 hom., cov: 33)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK1	NM_003565.4	c.246+4462C>T		intron_variant		ENST00000321867.6
ULK1	XM_011538798.4	c.246+4462C>T		intron_variant
ULK1	XM_011538799.3	c.246+4462C>T		intron_variant
ULK1	XR_007063134.1	n.626+4462C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK1	ENST00000321867.6	c.246+4462C>T		intron_variant		1	NM_003565.4	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96591 AN: 151994 Hom.: 34558 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.635 AC: 96600 AN: 152114 Hom.: 34552 Cov.: 33 AF XY: 0.626 AC XY: 46561 AN XY: 74342

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.677

Alfa AF: 0.695 Hom.: 5256

Bravo AF: 0.620

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.49

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: rs7953348; hg19: chr12-132384831;