rs34174194

Variant names:

• chr2-74458316-T-C
• rs34174194
• ENST00000452361.5:n.1067+456T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74458316-T-C
• chr2-74458316-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000452361.5(INO80B-WBP1):​n.1067+456T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000575 in 521,590 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: 0.0000058 (0 hom.)
• Consequence: INO80B-WBP1 ENST00000452361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80B-WBP1	NR_037849.1		n.1161+456T>C		intron	N/A
	WBP1	NM_012477.4	MANE Select	c.-287T>C		upstream_gene	N/A	NP_036609.1	Q96G27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80B-WBP1	ENST00000452361.5	TSL:2	n.1067+456T>C		intron	N/A	ENSP00000388677.1	J3KQ70
	INO80B-WBP1	ENST00000441673.2	TSL:5	n.745+778T>C		intron	N/A	ENSP00000392498.1	F8WCL7
	WBP1	ENST00000233615.7	TSL:1 MANE Select	c.-287T>C		upstream_gene	N/A	ENSP00000233615.2	Q96G27

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000575 AC: 3 AN: 521590 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 266610

African (AFR) AF: 0.00 AC: 0 AN: 13584

American (AMR) AF: 0.0000753 AC: 1 AN: 13284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12712

East Asian (EAS) AF: 0.0000712 AC: 2 AN: 28100

South Asian (SAS) AF: 0.00 AC: 0 AN: 34520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 363882

Other (OTH) AF: 0.00 AC: 0 AN: 27332

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		2.2
PromoterAI		-0.0055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34174194;

hg19: chr2-74685443;