NM_017553.3:c.928-137A>G

Variant names:

• chr15-41080041-T-C
• rs10518712
• NM_017553.3:c.928-137A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017553.3(INO80):​c.928-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 717,290 control chromosomes in the GnomAD database, including 1,776 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 0.074 (1223 hom., cov: 32)
  • Exomes 𝑓: 0.018 (553 hom.)
• Consequence: INO80 NM_017553.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 3 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]

INO80 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 1

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80	NM_017553.3	MANE Select	c.928-137A>G		intron	N/A	NP_060023.1
	INO80	NR_104038.2		n.1279-137A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80	ENST00000648947.1	MANE Select	c.928-137A>G		intron	N/A	ENSP00000497609.1
	INO80	ENST00000558357.6	TSL:1	n.928-137A>G		intron	N/A	ENSP00000453677.1
	INO80	ENST00000696949.1		n.928-137A>G		intron	N/A	ENSP00000512991.1

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11242 AN: 152106 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00753

Gnomad OTH AF: 0.0594

GnomAD4 exome AF: 0.0184 AC: 10395 AN: 565066 Hom.: 553 AF XY: 0.0186 AC XY: 5567 AN XY: 299808

African (AFR) AF: 0.236 AC: 3662 AN: 15546

American (AMR) AF: 0.0181 AC: 522 AN: 28870

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 701 AN: 16106

East Asian (EAS) AF: 0.0000306 AC: 1 AN: 32730

South Asian (SAS) AF: 0.0349 AC: 1946 AN: 55716

European-Finnish (FIN) AF: 0.000681 AC: 25 AN: 36728

Middle Eastern (MID) AF: 0.0402 AC: 90 AN: 2240

European-Non Finnish (NFE) AF: 0.00742 AC: 2575 AN: 347008

Other (OTH) AF: 0.0290 AC: 873 AN: 30122

GnomAD4 genome AF: 0.0741 AC: 11286 AN: 152224 Hom.: 1223 Cov.: 32 AF XY: 0.0717 AC XY: 5339 AN XY: 74430

African (AFR) AF: 0.238 AC: 9891 AN: 41514

American (AMR) AF: 0.0269 AC: 411 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0323 AC: 156 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00754 AC: 513 AN: 68012

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0562 Hom.: 114

Bravo AF: 0.0834

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.68
PhyloP100		-0.17
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: rs10518712; hg19: chr15-41372239;