rs773215331

Variant names:

• chr2-74455546-C-A
• NM_031288.4:c.199C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-74455546-C-A
• chr2-74455546-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031288.4(INO80B):​c.199C>A​(p.Pro67Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,564 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: INO80B NM_031288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28081366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80B	NM_031288.4	c.199C>A	p.Pro67Thr	missense_variant	Exon 2 of 5	ENST00000233331.12	NP_112578.2
INO80B-WBP1	NR_037849.1	n.293C>A		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80B	ENST00000233331.12	c.199C>A	p.Pro67Thr	missense_variant	Exon 2 of 5	1	NM_031288.4	ENSP00000233331.7
INO80B-WBP1	ENST00000452361.5	n.199C>A		non_coding_transcript_exon_variant	Exon 2 of 8	2		ENSP00000388677.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461564 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T;.;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.45	N;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;T
Polyphen		0.048	B;.;B;.
Vest4		0.48
MutPred		0.31		Gain of phosphorylation at P67 (P = 0.0126);Gain of phosphorylation at P67 (P = 0.0126);Gain of phosphorylation at P67 (P = 0.0126);.;
MVP		0.12
MPC		0.95
ClinPred		0.97	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74682673;