rs375852983

Variant names:

• chr2-74457706-C-A
• rs375852983
• NM_031288.4:c.913C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-74457706-C-A
• chr2-74457706-C-G
• chr2-74457706-C-T

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.913C>A​(p.Pro305Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P305L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: INO80B NM_031288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• 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=0.25693548).

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.913C>A	p.Pro305Thr	missense	Exon 5 of 5	NP_112578.2	Q9C086
	INO80B-WBP1	NR_037849.1		n.1007C>A		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.913C>A	p.Pro305Thr	missense	Exon 5 of 5	ENSP00000233331.7	Q9C086
	INO80B-WBP1	ENST00000452361.5	TSL:2	n.913C>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000388677.1	J3KQ70
	INO80B-WBP1	ENST00000441673.2	TSL:5	n.745+168C>A		intron	N/A	ENSP00000392498.1	F8WCL7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000441 AC: 1 AN: 226772 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447590 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720608

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111252

Other (OTH) AF: 0.00 AC: 0 AN: 60184

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00000835 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.042
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.086	T
Sift4G	Benign	0.18	T
Polyphen		0.76	P
Vest4		0.38
MVP		0.33
MPC		1.7
ClinPred		0.67	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.40
Mutation Taster		=72/28	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: rs375852983; hg19: chr2-74684833; COSMIC: COSV51970793; COSMIC: COSV51970793;