Genetic Variant PDE4DIP:p.Ala1272Ala (chr1-149002894-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001395426.1(PDE4DIP):c.3816G>A(p.Ala1272Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDE4DIP
NM_001395426.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0590

Publications

1 publications found

Variant links:

Genes affected

PDE4DIP (HGNC:15580): (phosphodiesterase 4D interacting protein) The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

PDE4DIP links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001395426.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-149002894-G-A is Benign according to our data. Variant chr1-149002894-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2639070.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.059 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395426.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE4DIP	NM_001395426.1	MANE Select	c.3816G>A	p.Ala1272Ala	synonymous	Exon 28 of 47	NP_001382355.1	A0A8Q3SI83
PDE4DIP	NM_001395297.1		c.4107G>A	p.Ala1369Ala	synonymous	Exon 21 of 40	NP_001382226.1
PDE4DIP	NM_001350520.2		c.4107G>A	p.Ala1369Ala	synonymous	Exon 21 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE4DIP	ENST00000695795.1	MANE Select	c.3816G>A	p.Ala1272Ala	synonymous	Exon 28 of 47	ENSP00000512175.1	A0A8Q3SI83
PDE4DIP	ENST00000369356.8	TSL:1	c.3618G>A	p.Ala1206Ala	synonymous	Exon 25 of 44	ENSP00000358363.4	Q5VU43-4
PDE4DIP	ENST00000369354.7	TSL:1	c.3618G>A	p.Ala1206Ala	synonymous	Exon 25 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes

AF:

0.0000422

AC:

AN:

142292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000212

Gnomad SAS

AF:

0.000254

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000306

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000135

AC:

AN:

251322

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000481

AC:

AN:

499374

Hom.:

Cov.:

AF XY:

0.0000529

AC XY:

AN XY:

264852

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13460

American (AMR)

AF:

0.000207

AC:

AN:

24148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14186

East Asian (EAS)

AF:

0.0000915

AC:

AN:

32770

South Asian (SAS)

AF:

0.0000203

AC:

AN:

49280

European-Finnish (FIN)

AF:

0.0000236

AC:

AN:

42438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2096

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

293482

Other (OTH)

AF:

0.00

AC:

AN:

27514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000421

AC:

AN:

142410

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

68910

show subpopulations

African (AFR)

AF:

0.0000527

AC:

AN:

37964

American (AMR)

AF:

0.00

AC:

AN:

14116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3352

East Asian (EAS)

AF:

0.000212

AC:

AN:

4706

South Asian (SAS)

AF:

0.000254

AC:

AN:

3930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

65456

Other (OTH)

AF:

0.00

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000188

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.6

(source)

DANN

Benign

0.57

PhyloP100

-0.059

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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