15-40982816-T-G

Variant names:

• chr15-40982816-T-G
• rs7173954
• NM_017553.3:c.4453+46A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017553.3(INO80):​c.4453+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,462,156 control chromosomes in the GnomAD database, including 94,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9038 hom., cov: 32)
  • Exomes 𝑓: 0.35 (85111 hom.)
• Consequence: INO80 NM_017553.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270

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]

LOC124903476 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-40982816-T-G is Benign according to our data. Variant chr15-40982816-T-G is described in ClinVar as [Benign]. Clinvar id is 2688187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80	NM_017553.3	c.4453+46A>C		intron_variant	Intron 35 of 35	ENST00000648947.1	NP_060023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1	c.4453+46A>C		intron_variant	Intron 35 of 35		NM_017553.3	ENSP00000497609.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50798 AN: 152040 Hom.: 9037 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.335

GnomAD3 exomes AF: 0.307 AC: 68474 AN: 223256 Hom.: 12157 AF XY: 0.311 AC XY: 37758 AN XY: 121590

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.00474

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.351 AC: 459295 AN: 1309998 Hom.: 85111 Cov.: 18 AF XY: 0.349 AC XY: 227185 AN XY: 651704

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.00403

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.334 AC: 50821 AN: 152158 Hom.: 9038 Cov.: 32 AF XY: 0.331 AC XY: 24627 AN XY: 74396

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.00791

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.333

Alfa AF: 0.338 Hom.: 5315

Bravo AF: 0.327

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 39% of patients studied by a panel of primary immunodeficiencies. Number of patients: 37. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.6
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7173954; hg19: chr15-41275014;