rs4964879

Positions:

• chr12-131915764-G-A
• chr12-131915764-G-C

Variant summary

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

The NM_003565.4(ULK1):​c.1610-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,326,766 control chromosomes in the GnomAD database, including 22,896 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 0.22 (5083 hom., cov: 33)
  • Exomes 𝑓: 0.14 (17813 hom.)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK1	NM_003565.4	c.1610-127G>A		intron_variant		ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.1679-127G>A		intron_variant			XP_011537100.1
ULK1	XM_011538799.3	c.1592-127G>A		intron_variant			XP_011537101.1
ULK1	XR_007063134.1	n.2059-127G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.1610-127G>A		intron_variant		1	NM_003565.4	ENSP00000324560	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33147 AN: 151946 Hom.: 5085 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.143 AC: 168288 AN: 1174702 Hom.: 17813 AF XY: 0.141 AC XY: 83142 AN XY: 589346

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.0799

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.218 AC: 33162 AN: 152064 Hom.: 5083 Cov.: 33 AF XY: 0.219 AC XY: 16279 AN XY: 74324

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.182

Alfa AF: 0.134 Hom.: 1689

Bravo AF: 0.231

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.57

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: rs4964879; hg19: chr12-132400309; COSMIC: COSV58854458; COSMIC: COSV58854458;