ENST00000452361.5:n.1067+398C>A

Variant names:

• chr2-74458229-T-A
• rs188586448
• ENST00000452361.5:n.1067+369T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000452361.5(INO80B-WBP1):​n.1067+369T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000721 in 277,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: INO80B-WBP1 ENST00000452361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

Genes affected

INO80B-WBP1 (HGNC:49199): (INO80B-WBP1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring INO80B (INO80 complex subunit B) and WBP1 (WW domain-binding protein 1) genes on chromosome 2. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

WBP1 (HGNC:12737): (WW domain binding protein 1) The globular WW domain, named for the conserved tryptophan residues in the protein motif present in various structural and regulatory proteins, is known to play a role in the mediation of protein-protein interactions. This gene encodes a ligand of the WW domain of the Yes kinase-associated protein. Readthrough transcription of the neighboring upstream gene, which encodes INO80 complex subunit B, into this gene generates a non-coding transcript. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452361.5. 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
	INO80B-WBP1	NR_037849.1		n.1161+369T>A		intron	N/A
	WBP1	NM_012477.4	MANE Select	c.-374T>A		upstream_gene	N/A	NP_036609.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80B-WBP1	ENST00000452361.5	TSL:2	n.1067+369T>A		intron	N/A	ENSP00000388677.1
	INO80B-WBP1	ENST00000441673.2	TSL:5	n.745+691T>A		intron	N/A	ENSP00000392498.1
	WBP1	ENST00000233615.7	TSL:1 MANE Select	c.-374T>A		upstream_gene	N/A	ENSP00000233615.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000721 AC: 2 AN: 277402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 142710

African (AFR) AF: 0.000133 AC: 1 AN: 7500

American (AMR) AF: 0.00 AC: 0 AN: 9270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9582

East Asian (EAS) AF: 0.0000471 AC: 1 AN: 21238

South Asian (SAS) AF: 0.00 AC: 0 AN: 15726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1320

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 174788

Other (OTH) AF: 0.00 AC: 0 AN: 17656

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-1.5
PromoterAI		-0.0052	Neutral

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: rs188586448; hg19: chr2-74685356;