12-131902684-T-C

Position:

• chr12-131902684-T-C

Variant summary

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

The ENST00000321867.6(ULK1):​c.247-4208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,914 control chromosomes in the GnomAD database, including 5,069 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 0.19 (5069 hom., cov: 32)
• Consequence: ULK1 ENST00000321867.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK1	NM_003565.4	c.247-4208T>C		intron_variant		ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.247-4208T>C		intron_variant			XP_011537100.1
ULK1	XM_011538799.3	c.247-4208T>C		intron_variant			XP_011537101.1
ULK1	XR_007063134.1	n.627-4208T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.247-4208T>C		intron_variant		1	NM_003565.4	ENSP00000324560	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28311 AN: 151796 Hom.: 5068 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.187 AC: 28342 AN: 151914 Hom.: 5069 Cov.: 32 AF XY: 0.184 AC XY: 13633 AN XY: 74268

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0727

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0699 Hom.: 245

Bravo AF: 0.201

Asia WGS AF: 0.111 AC: 388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.52

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: rs7488085; hg19: chr12-132387229;