chr2-74457607-A-G

Variant names:

• chr2-74457607-A-G
• rs368166183
• NM_031288.4:c.814A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031288.4(INO80B):​c.814A>G​(p.Met272Val) variant causes a missense change. The variant allele was found at a frequency of 0.000098 in 1,560,982 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. M272R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000089 (1 hom.)
• Consequence: INO80B NM_031288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011286825).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031288.4. 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	NM_031288.4	MANE Select	c.814A>G	p.Met272Val	missense	Exon 5 of 5	NP_112578.2	Q9C086
	INO80B-WBP1	NR_037849.1		n.908A>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80B	ENST00000233331.12	TSL:1 MANE Select	c.814A>G	p.Met272Val	missense	Exon 5 of 5	ENSP00000233331.7	Q9C086
	INO80B-WBP1	ENST00000452361.5	TSL:2	n.814A>G		non_coding_transcript_exon	Exon 5 of 8	ENSP00000388677.1	J3KQ70
	INO80B	ENST00000409917.5	TSL:2	c.*171A>G		3_prime_UTR	Exon 5 of 5	ENSP00000387267.1	B8ZZ93

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 151964 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000266 AC: 45 AN: 169490 AF XY: 0.000264

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00259

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000894 AC: 126 AN: 1408906 Hom.: 1 Cov.: 33 AF XY: 0.000100 AC XY: 70 AN XY: 698198

African (AFR) AF: 0.0000318 AC: 1 AN: 31402

American (AMR) AF: 0.00 AC: 0 AN: 39128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24760

East Asian (EAS) AF: 0.00122 AC: 45 AN: 37020

South Asian (SAS) AF: 0.000601 AC: 49 AN: 81540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4540

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1092112

Other (OTH) AF: 0.000462 AC: 27 AN: 58442

GnomAD4 genome AF: 0.000178 AC: 27 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5162

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.000188 AC: 22

Asia WGS AF: 0.00636 AC: 22 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Benign	0.38	T
Sift4G	Benign	0.51	T
Polyphen		0.20	B
Vest4		0.62
MutPred		0.57		Gain of sheet (P = 0.0221)
MVP		0.55
MPC		0.68
ClinPred		0.15	T
GERP RS		4.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.64
gMVP		0.47
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: rs368166183; hg19: chr2-74684734; COSMIC: COSV51969538; COSMIC: COSV51969538;