Genetic Variant IPO4:c.278+196G>A (chr14-24188020-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024658.4(IPO4):c.278+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 767,480 control chromosomes in the GnomAD database, including 38,835 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 0.31 ( 7277 hom., cov: 32)

Exomes 𝑓: 0.31 ( 31558 hom. )

Consequence

IPO4
NM_024658.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.554

Publications

17 publications found

Variant links:

Genes affected

IPO4 (HGNC:19426): (importin 4) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Involved in DNA replication-dependent chromatin assembly; DNA replication-independent chromatin assembly; and protein import into nucleus. Located in chromatin. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

IPO4 links:

ENSG00000259522 (HGNC:):

ENSG00000259522 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO4	NM_024658.4 link	c.278+196G>A		intron_variant	Intron 4 of 29	ENST00000354464.11	NP_078934.3	Q8TEX9-1B3KT38
IPO4	NR_051979.2 link	n.307+196G>A		intron_variant	Intron 4 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO4	ENST00000354464.11 link	c.278+196G>A		intron_variant	Intron 4 of 29	1	NM_024658.4	ENSP00000346453.6		Q8TEX9-1
ENSG00000259522	ENST00000561419.1 link	n.*905+196G>A		intron_variant	Intron 5 of 30	2		ENSP00000454374.1		H3BMG7

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46675

AN:

151918

Hom.:

7268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.313

AC:

192628

AN:

615444

Hom.:

31558

Cov.:

AF XY:

0.317

AC XY:

101316

AN XY:

319526

show subpopulations

African (AFR)

AF:

0.322

AC:

5019

AN:

15602

American (AMR)

AF:

0.295

AC:

6925

AN:

23512

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

3188

AN:

15650

East Asian (EAS)

AF:

0.462

AC:

14835

AN:

32102

South Asian (SAS)

AF:

0.411

AC:

20977

AN:

51044

European-Finnish (FIN)

AF:

0.215

AC:

7261

AN:

33738

Middle Eastern (MID)

AF:

0.227

AC:

654

AN:

2878

European-Non Finnish (NFE)

AF:

0.303

AC:

124155

AN:

409316

Other (OTH)

AF:

0.304

AC:

9614

AN:

31602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

7099

14198

21297

28396

35495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2274

4548

6822

9096

11370

<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:

0.307

AC:

46723

AN:

152036

Hom.:

7277

Cov.:

AF XY:

0.305

AC XY:

22632

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.324

AC:

13426

AN:

41444

American (AMR)

AF:

0.291

AC:

4441

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

712

AN:

3470

East Asian (EAS)

AF:

0.425

AC:

2195

AN:

5170

South Asian (SAS)

AF:

0.421

AC:

2028

AN:

4816

European-Finnish (FIN)

AF:

0.215

AC:

2277

AN:

10576

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20693

AN:

67964

Other (OTH)

AF:

0.286

AC:

603

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1656

3311

4967

6622

8278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.303

Hom.:

22243

Bravo

AF:

0.313

Asia WGS

AF:

0.461

AC:

1601

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over