Genetic Variant INO80:c.4453+46A>C (chr15-40982816-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.270

Publications

9 publications found

Variant links:

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

INO80 links:

LOC124903476 (HGNC:):

LOC124903476 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80	NM_017553.3	MANE Select	c.4453+46A>C		intron	N/A	NP_060023.1	Q9ULG1
	INO80	NR_104038.2		n.4676+46A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INO80	ENST00000648947.1	MANE Select	c.4453+46A>C	intron	N/A	ENSP00000497609.1	Q9ULG1
INO80	ENST00000558357.6	TSL:1	n.*1010+46A>C	intron	N/A	ENSP00000453677.1	H0YMN5
INO80	ENST00000933337.1		c.4453+46A>C	intron	N/A	ENSP00000603396.1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50798

AN:

152040

Hom.:

9037

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.349

AC XY:

227185

AN XY:

651704

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14306

28613

42919

57226

71532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11350

22700

34050

45400

56750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.334

AC:

50821

AN:

152158

Hom.:

9038

Cov.:

AF XY:

0.331

AC XY:

24627

AN XY:

74396

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1721

3442

5162

6883

8604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.350

Hom.:

17525

Bravo

AF:

0.327

Asia WGS

AF:

0.159

AC:

556

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

(source)

DANN

Benign

0.76

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over