Genetic Variant AAGAB:c.452-715A>G (chr15-67232612-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_024666.5(AAGAB):c.452-715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 377,674 control chromosomes in the GnomAD database, including 33,580 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 0.45 ( 15946 hom., cov: 32)

Exomes 𝑓: 0.37 ( 17634 hom. )

Consequence

AAGAB
NM_024666.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

Publications

10 publications found

Variant links:

Genes affected

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

AAGAB links:

RPS24P16 (HGNC:35542): (ribosomal protein S24 pseudogene 16)

RPS24P16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AAGAB	NM_024666.5	MANE Select	c.452-715A>G	intron	N/A	NP_078942.3
AAGAB	NM_001271885.2		c.125-715A>G	intron	N/A	NP_001258814.1	Q6PD74-2
AAGAB	NM_001271886.2		c.125-715A>G	intron	N/A	NP_001258815.1	Q6PD74-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AAGAB	ENST00000261880.10	TSL:1 MANE Select	c.452-715A>G	intron	N/A	ENSP00000261880.5	Q6PD74-1
AAGAB	ENST00000947778.1		c.452-715A>G	intron	N/A	ENSP00000617837.1
AAGAB	ENST00000902812.1		c.452-727A>G	intron	N/A	ENSP00000572871.1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68596

AN:

151962

Hom.:

15945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.372

AC:

83971

AN:

225594

Hom.:

17634

Cov.:

AF XY:

0.371

AC XY:

48449

AN XY:

130696

show subpopulations

African (AFR)

AF:

0.323

AC:

1930

AN:

5982

American (AMR)

AF:

0.194

AC:

5138

AN:

26436

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

2434

AN:

7078

East Asian (EAS)

AF:

0.130

AC:

1210

AN:

9340

South Asian (SAS)

AF:

0.266

AC:

10337

AN:

38872

European-Finnish (FIN)

AF:

0.492

AC:

5412

AN:

10992

Middle Eastern (MID)

AF:

0.391

AC:

290

AN:

742

European-Non Finnish (NFE)

AF:

0.458

AC:

53026

AN:

115852

Other (OTH)

AF:

0.407

AC:

4194

AN:

10300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

1977

3953

5930

7906

9883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.451

AC:

68609

AN:

152080

Hom.:

15946

Cov.:

AF XY:

0.446

AC XY:

33168

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.407

AC:

16871

AN:

41460

American (AMR)

AF:

0.346

AC:

5284

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1453

AN:

3470

East Asian (EAS)

AF:

0.193

AC:

999

AN:

5184

South Asian (SAS)

AF:

0.325

AC:

1566

AN:

4818

European-Finnish (FIN)

AF:

0.526

AC:

5555

AN:

10566

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35397

AN:

67984

Other (OTH)

AF:

0.429

AC:

905

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1937

3875

5812

7750

9687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.452

Hom.:

2775

Bravo

AF:

0.434

Asia WGS

AF:

0.253

AC:

881

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

2.9

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