2-74458316-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000452361.5(INO80B-WBP1):​n.1067+456T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 673,140 control chromosomes in the GnomAD database, including 7,759 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 0.11 (1371 hom., cov: 33)
  • Exomes 𝑓: 0.14 (6388 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

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>G		intron	N/A
	WBP1	NM_012477.4	MANE Select	c.-287T>G		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>G		intron	N/A	ENSP00000388677.1	J3KQ70
	INO80B-WBP1	ENST00000441673.2	TSL:5	n.745+778T>G		intron	N/A	ENSP00000392498.1	F8WCL7
	WBP1	ENST00000233615.7	TSL:1 MANE Select	c.-287T>G		upstream_gene	N/A	ENSP00000233615.2	Q96G27

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16955 AN: 152118 Hom.: 1372 Cov.: 33

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.143 AC: 74469 AN: 520904 Hom.: 6388 Cov.: 7 AF XY: 0.140 AC XY: 37214 AN XY: 266250

African (AFR) AF: 0.0276 AC: 375 AN: 13574

American (AMR) AF: 0.0660 AC: 876 AN: 13276

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1439 AN: 12700

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

South Asian (SAS) AF: 0.0361 AC: 1247 AN: 34510

European-Finnish (FIN) AF: 0.244 AC: 6373 AN: 26140

Middle Eastern (MID) AF: 0.0967 AC: 194 AN: 2006

European-Non Finnish (NFE) AF: 0.166 AC: 60445 AN: 363306

Other (OTH) AF: 0.129 AC: 3518 AN: 27292

GnomAD4 genome AF: 0.111 AC: 16947 AN: 152236 Hom.: 1371 Cov.: 33 AF XY: 0.111 AC XY: 8288 AN XY: 74424

African (AFR) AF: 0.0274 AC: 1138 AN: 41554

American (AMR) AF: 0.0693 AC: 1059 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2650 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11209 AN: 68010

Other (OTH) AF: 0.106 AC: 224 AN: 2106

Alfa AF: 0.126 Hom.: 2423

Bravo AF: 0.0941

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		2.2
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism

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: rs34174194;

hg19: chr2-74685443;