rs4964879

Variant names:

• chr12-131915764-G-A
• rs4964879
• NM_003565.4:c.1610-127G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	NM_003565.4	MANE Select	c.1610-127G>A		intron	N/A	NP_003556.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	ENST00000321867.6	TSL:1 MANE Select	c.1610-127G>A		intron	N/A	ENSP00000324560.3
	ULK1	ENST00000541761.2	TSL:2	n.-179G>A		upstream_gene	N/A

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

African (AFR) AF: 0.396 AC: 10305 AN: 26052

American (AMR) AF: 0.224 AC: 6170 AN: 27534

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 1726 AN: 21600

East Asian (EAS) AF: 0.615 AC: 22579 AN: 36734

South Asian (SAS) AF: 0.123 AC: 8827 AN: 72034

European-Finnish (FIN) AF: 0.155 AC: 5555 AN: 35724

Middle Eastern (MID) AF: 0.0853 AC: 350 AN: 4104

European-Non Finnish (NFE) AF: 0.117 AC: 104920 AN: 900486

Other (OTH) AF: 0.156 AC: 7856 AN: 50434

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

African (AFR) AF: 0.392 AC: 16242 AN: 41466

American (AMR) AF: 0.181 AC: 2775 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.580 AC: 2986 AN: 5146

South Asian (SAS) AF: 0.135 AC: 650 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1656 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8106 AN: 67962

Other (OTH) AF: 0.182 AC: 385 AN: 2112

Alfa AF: 0.145 Hom.: 2674

Bravo AF: 0.231

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.57
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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