NM_017553.3:c.-44+6621C>T

Variant names:

• chr15-41109352-G-A
• rs2928148
• NM_017553.3:c.-44+6621C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

CYCSP2 (HGNC:24410): (CYCS pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
INO80	NM_017553.3	c.-44+6621C>T		intron_variant	Intron 1 of 35	ENST00000648947.1	NP_060023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1	c.-44+6621C>T		intron_variant	Intron 1 of 35		NM_017553.3	ENSP00000497609.1
INO80	ENST00000558357.6	n.-44+6621C>T		intron_variant	Intron 1 of 34	1		ENSP00000453677.1
INO80	ENST00000696949.1	n.-44+6621C>T		intron_variant	Intron 1 of 33			ENSP00000512991.1
CYCSP2	ENST00000558168.1	n.*174G>A		downstream_gene_variant		6

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

African (AFR) AF: 0.201 AC: 8327 AN: 41422

American (AMR) AF: 0.536 AC: 8183 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1636 AN: 3460

East Asian (EAS) AF: 0.695 AC: 3563 AN: 5130

South Asian (SAS) AF: 0.472 AC: 2265 AN: 4800

European-Finnish (FIN) AF: 0.632 AC: 6665 AN: 10552

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35492 AN: 67914

Other (OTH) AF: 0.460 AC: 969 AN: 2108

Alfa AF: 0.462 Hom.: 2313

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
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs2928148; hg19: chr15-41401550;