rs2928148

Positions:

• chr15-41109352-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017553.3(INO80):​c.-44+6621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,846 control chromosomes in the GnomAD database, including 17,008 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 0.45 (17008 hom., cov: 31)
• Consequence: INO80 NM_017553.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

Genes affected

INO80 (HGNC:26956): (INO80 complex ATPase subunit) This gene encodes a subunit of the chromatin remodeling complex, which is classified into subfamilies depending on sequence features apart from the conserved ATPase domain. This protein is the catalytic ATPase subunit of the INO80 chromatin remodeling complex, which is characterized by a DNA-binding domain. This protein is proposed to bind DNA and be recruited by the YY1 transcription factor to activate certain genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INO80	NM_017553.3	c.-44+6621C>T		intron_variant		ENST00000648947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INO80	ENST00000648947.1	c.-44+6621C>T		intron_variant			NM_017553.3	P1
INO80	ENST00000558357.6	c.-44+6621C>T		intron_variant, NMD_transcript_variant		1
INO80	ENST00000696949.1	c.-44+6621C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67651 AN: 151728 Hom.: 17007 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67653 AN: 151846 Hom.: 17008 Cov.: 31 AF XY: 0.452 AC XY: 33572 AN XY: 74204

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.460

Alfa AF: 0.471 Hom.: 2292

Bravo AF: 0.431

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2928148; hg19: chr15-41401550;