15-40982816-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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

LOC124903476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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

GnomAD2 exomes AF: 0.307 AC: 68474 AN: 223256 AF XY: 0.311

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 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

African (AFR) AF: 0.329 AC: 9809 AN: 29792

American (AMR) AF: 0.199 AC: 7632 AN: 38396

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 9803 AN: 23566

East Asian (EAS) AF: 0.00403 AC: 155 AN: 38486

South Asian (SAS) AF: 0.269 AC: 21256 AN: 79058

European-Finnish (FIN) AF: 0.370 AC: 18690 AN: 50454

Middle Eastern (MID) AF: 0.389 AC: 1468 AN: 3772

European-Non Finnish (NFE) AF: 0.375 AC: 372127 AN: 991800

Other (OTH) AF: 0.336 AC: 18355 AN: 54674

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

African (AFR) AF: 0.330 AC: 13686 AN: 41502

American (AMR) AF: 0.268 AC: 4095 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3468

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5186

South Asian (SAS) AF: 0.240 AC: 1161 AN: 4830

European-Finnish (FIN) AF: 0.367 AC: 3892 AN: 10592

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25161 AN: 67970

Other (OTH) AF: 0.333 AC: 704 AN: 2112

Alfa AF: 0.350 Hom.: 17525

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
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7173954; hg19: chr15-41275014;