rs1880480

Variant names:

• chr3-41252216-T-A
• rs1880480
• NM_017886.4:c.3679-2642A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-41252216-T-A
• chr3-41252216-T-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.3679-2642A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,056 control chromosomes in the GnomAD database, including 24,511 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 0.56 (24511 hom., cov: 32)
• Consequence: ULK4 NM_017886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 3 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):

• exudative vitreoretinopathy

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

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3679-2642A>T		intron_variant	Intron 35 of 36	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3679-2642A>T		intron_variant	Intron 35 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000489118.1	n.347-1092A>T		intron_variant	Intron 1 of 3	1
CTNNB1	ENST00000471014.2	n.*13-6116T>A		intron_variant	Intron 4 of 5	3		ENSP00000495552.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85035 AN: 151938 Hom.: 24481 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.560 AC: 85112 AN: 152056 Hom.: 24511 Cov.: 32 AF XY: 0.560 AC XY: 41594 AN XY: 74300

African (AFR) AF: 0.690 AC: 28611 AN: 41472

American (AMR) AF: 0.549 AC: 8382 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1536 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2279 AN: 5170

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4818

European-Finnish (FIN) AF: 0.535 AC: 5648 AN: 10554

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34204 AN: 67988

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.518 Hom.: 2496

Bravo AF: 0.566

Asia WGS AF: 0.557 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		0.078
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: rs1880480; hg19: chr3-41293707;