rs10518712

Positions:

• chr15-41080041-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INO80	NM_017553.3	c.928-137A>G		intron_variant		ENST00000648947.1	NP_060023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1	c.928-137A>G		intron_variant			NM_017553.3	ENSP00000497609	P1
INO80	ENST00000558357.6	c.928-137A>G		intron_variant, NMD_transcript_variant		1		ENSP00000453677
INO80	ENST00000696949.1	c.928-137A>G		intron_variant, NMD_transcript_variant				ENSP00000512991

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

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0435

Gnomad4 EAS exome AF: 0.0000306

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.000681

Gnomad4 NFE exome AF: 0.00742

Gnomad4 OTH exome AF: 0.0290

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

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00754

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0494 Hom.: 97

Bravo AF: 0.0834

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.68

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: rs10518712; hg19: chr15-41372239;