Genetic Variant AKIP1:c.489+20C>T (chr11-8917387-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_020642.4(AKIP1):c.489+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,600,172 control chromosomes in the GnomAD database, including 94,047 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 0.28 ( 6937 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87110 hom. )

Consequence

AKIP1
NM_020642.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

14 publications found

Variant links:

Genes affected

AKIP1 (HGNC:1170): (A-kinase interacting protein 1) This gene encodes a nuclear protein that interacts with protein kinase A catalytic subunit, and regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

AKIP1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=3.97712E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020642.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKIP1	NM_020642.4	MANE Select	c.489+20C>T	intron	N/A	NP_065693.2
AKIP1	NM_001206646.2		c.408+20C>T	intron	N/A	NP_001193575.1	Q9NQ31-3
AKIP1	NM_001206647.2		c.409-1950C>T	intron	N/A	NP_001193576.1	Q9NQ31-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKIP1	ENST00000309377.9	TSL:1 MANE Select	c.489+20C>T	intron	N/A	ENSP00000310459.4	Q9NQ31-1
AKIP1	ENST00000534147.5	TSL:1	c.489+20C>T	intron	N/A	ENSP00000431331.1	Q9NQ31-1
AKIP1	ENST00000299576.9	TSL:1	c.408+20C>T	intron	N/A	ENSP00000299576.5	Q9NQ31-3

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42799

AN:

151978

Hom.:

6932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.323

AC:

79976

AN:

247298

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.341

AC:

494067

AN:

1448074

Hom.:

87110

Cov.:

AF XY:

0.346

AC XY:

249597

AN XY:

721042

show subpopulations

African (AFR)

AF:

0.116

AC:

3838

AN:

33144

American (AMR)

AF:

0.240

AC:

10679

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

11637

AN:

25974

East Asian (EAS)

AF:

0.173

AC:

6866

AN:

39612

South Asian (SAS)

AF:

0.439

AC:

37616

AN:

85690

European-Finnish (FIN)

AF:

0.303

AC:

16082

AN:

53080

Middle Eastern (MID)

AF:

0.422

AC:

2421

AN:

5738

European-Non Finnish (NFE)

AF:

0.349

AC:

384383

AN:

1100392

Other (OTH)

AF:

0.343

AC:

20545

AN:

59952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

15127

30254

45380

60507

75634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12082

24164

36246

48328

60410

<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:

0.281

AC:

42813

AN:

152098

Hom.:

6937

Cov.:

AF XY:

0.282

AC XY:

20924

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.126

AC:

5244

AN:

41520

American (AMR)

AF:

0.272

AC:

4162

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

1569

AN:

3470

East Asian (EAS)

AF:

0.216

AC:

1119

AN:

5172

South Asian (SAS)

AF:

0.439

AC:

2116

AN:

4816

European-Finnish (FIN)

AF:

0.311

AC:

3285

AN:

10562

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24201

AN:

67970

Other (OTH)

AF:

0.312

AC:

656

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1467

2934

4401

5868

7335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.332

Hom.:

3324

Bravo

AF:

0.267

TwinsUK

AF:

0.344

AC:

1276

ALSPAC

AF:

0.359

AC:

1384

ESP6500AA

AF:

0.133

AC:

586

ESP6500EA

AF:

0.355

AC:

3046

ExAC

AF:

0.324

AC:

39280

Asia WGS

AF:

0.324

AC:

1130

AN:

3478

EpiCase

AF:

0.377

EpiControl

AF:

0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.22

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.35

MetaRNN

Benign

0.00040

MetaSVM

Benign

-0.93

PhyloP100

-1.6

PROVEAN

Benign

-0.70

REVEL

Benign

0.0050

Sift

Benign

0.24

Sift4G

Pathogenic

0.0

Polyphen

0.010

Vest4

0.17

ClinPred

0.0024

GERP RS

-5.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over