12-131899081-A-G

Variant names:

• chr12-131899081-A-G
• rs7133672
• NM_003565.4:c.246+3257A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003565.4(ULK1):​c.246+3257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 150,900 control chromosomes in the GnomAD database, including 13,108 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 0.35 (13108 hom., cov: 30)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.246+3257A>G		intron_variant	Intron 3 of 27	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.246+3257A>G		intron_variant	Intron 3 of 27		XP_011537100.1
ULK1	XM_011538799.3	c.246+3257A>G		intron_variant	Intron 3 of 27		XP_011537101.1
ULK1	XR_007063134.1	n.626+3257A>G		intron_variant	Intron 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.246+3257A>G		intron_variant	Intron 3 of 27	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53268 AN: 150784 Hom.: 13095 Cov.: 30

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0982

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.353 AC: 53343 AN: 150900 Hom.: 13108 Cov.: 30 AF XY: 0.364 AC XY: 26780 AN XY: 73634

African (AFR) AF: 0.667 AC: 27495 AN: 41248

American (AMR) AF: 0.306 AC: 4600 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 795 AN: 3460

East Asian (EAS) AF: 0.686 AC: 3517 AN: 5124

South Asian (SAS) AF: 0.332 AC: 1585 AN: 4778

European-Finnish (FIN) AF: 0.328 AC: 3374 AN: 10274

Middle Eastern (MID) AF: 0.234 AC: 66 AN: 282

European-Non Finnish (NFE) AF: 0.165 AC: 11164 AN: 67686

Other (OTH) AF: 0.315 AC: 658 AN: 2090

Alfa AF: 0.176 Hom.: 644

Bravo AF: 0.367

Asia WGS AF: 0.503 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.14
PhyloP100		-1.2
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: rs7133672; hg19: chr12-132383626;