rs11129896

Variant names:

• chr3-41254276-T-C
• rs11129896
• NM_017886.4:c.3679-4702A>G

Variant summary

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

The NM_017886.4(ULK4):​c.3679-4702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,062 control chromosomes in the GnomAD database, including 10,273 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 0.34 (10273 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.08
• Publications: 13 publications found

Genes affected

ULK4 (HGNC:15784): (unc-51 like kinase 4) This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

CTNNB1 Gene-Disease associations (from GenCC):

• CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• exudative vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• severe intellectual disability-progressive spastic diplegia syndrome

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Illumina, Labcorp Genetics (formerly Invitae)
• exudative vitreoretinopathy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.3679-4702A>G		intron	N/A	NP_060356.2	Q96C45
	ULK4	NM_001322501.2		c.2773-4702A>G		intron	N/A	NP_001309430.1
	ULK4	NR_136342.2		n.3650-4702A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.3679-4702A>G		intron	N/A	ENSP00000301831.4	Q96C45
	ULK4	ENST00000489118.1	TSL:1	n.347-3152A>G		intron	N/A
	ULK4	ENST00000951851.1		c.3676-4702A>G		intron	N/A	ENSP00000621910.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51417 AN: 151944 Hom.: 10274 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.338 AC: 51417 AN: 152062 Hom.: 10273 Cov.: 32 AF XY: 0.338 AC XY: 25101 AN XY: 74326

African (AFR) AF: 0.123 AC: 5101 AN: 41494

American (AMR) AF: 0.411 AC: 6275 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1475 AN: 3466

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5184

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4505 AN: 10542

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29913 AN: 67960

Other (OTH) AF: 0.346 AC: 730 AN: 2108

Alfa AF: 0.401 Hom.: 27668

Bravo AF: 0.329

Asia WGS AF: 0.331 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.058
DANN	Benign	0.57
PhyloP100		-5.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11129896;

hg19: chr3-41295767;