rs10902472

Variant names:

• chr12-131903013-C-T
• rs10902472
• NM_003565.4:c.247-3879C>T

Variant summary

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

The NM_003565.4(ULK1):​c.247-3879C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,082 control chromosomes in the GnomAD database, including 4,788 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 0.18 (4788 hom., cov: 32)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.247-3879C>T		intron_variant	Intron 3 of 27	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.247-3879C>T		intron_variant	Intron 3 of 27		XP_011537100.1
ULK1	XM_011538799.3	c.247-3879C>T		intron_variant	Intron 3 of 27		XP_011537101.1
ULK1	XR_007063134.1	n.627-3879C>T		intron_variant	Intron 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.247-3879C>T		intron_variant	Intron 3 of 27	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 151964 Hom.: 4787 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.182 AC: 27738 AN: 152082 Hom.: 4788 Cov.: 32 AF XY: 0.179 AC XY: 13338 AN XY: 74346

African (AFR) AF: 0.456 AC: 18892 AN: 41432

American (AMR) AF: 0.103 AC: 1576 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3472

East Asian (EAS) AF: 0.0729 AC: 377 AN: 5168

South Asian (SAS) AF: 0.117 AC: 562 AN: 4806

European-Finnish (FIN) AF: 0.0762 AC: 809 AN: 10614

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4609 AN: 67984

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.0941 Hom.: 1354

Bravo AF: 0.196

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		-3.7
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: rs10902472; hg19: chr12-132387558;