chr2-74457595-G-C

Variant names:

• chr2-74457595-G-C
• rs1316744396
• NM_031288.4:c.802G>C

Variant summary

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

The NM_031288.4(INO80B):​c.802G>C​(p.Ala268Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A268T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: INO80B NM_031288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

Genes affected

INO80B (HGNC:13324): (INO80 complex subunit B) This gene encodes a subunit of an ATP-dependent chromatin remodeling complex, INO80, which plays a role in DNA and nucleosome-activated ATPase activity and ATP-dependent nucleosome sliding. Readthrough transcription of this gene into the neighboring downstream gene, which encodes WW domain-binding protein 1, generates a non-coding transcript. [provided by RefSeq, Feb 2011]

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]

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 (MetaRNN=0.24131545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80B	NM_031288.4	c.802G>C	p.Ala268Pro	missense_variant	Exon 5 of 5	ENST00000233331.12	NP_112578.2
INO80B-WBP1	NR_037849.1	n.896G>C		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80B	ENST00000233331.12	c.802G>C	p.Ala268Pro	missense_variant	Exon 5 of 5	1	NM_031288.4	ENSP00000233331.7
INO80B-WBP1	ENST00000452361.5	n.802G>C		non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000388677.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
PhyloP100		5.7
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.17
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.96	D
Vest4		0.27
MutPred		0.49		Gain of catalytic residue at A268 (P = 0.0053);
MVP		0.29
MPC		0.83
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.35
gMVP		0.32
Mutation Taster		=81/19	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

Other links and lift over

dbSNP: rs1316744396; hg19: chr2-74684722;