1-148893214-A-T

Variant names:

• chr1-148893214-A-T
• rs1778596
• NM_001395426.1:c.339+3320A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395426.1(PDE4DIP):​c.339+3320A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 120,324 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0039 (0 hom., cov: 21)
• Consequence: PDE4DIP NM_001395426.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	NM_001395426.1	MANE Select	c.339+3320A>T		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001377392.2		c.552+3320A>T		intron	N/A	NP_001364321.1	A0A8Q3WM32
	PDE4DIP	NM_001395298.1		c.552+3320A>T		intron	N/A	NP_001382227.1	A0A075B749

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000695795.1	MANE Select	c.339+3320A>T		intron	N/A	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.141+3320A>T		intron	N/A	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.141+3320A>T		intron	N/A	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 462 AN: 120282 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00371

Gnomad AMI AF: 0.00259

Gnomad AMR AF: 0.00672

Gnomad ASJ AF: 0.00272

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.00223

Gnomad FIN AF: 0.00324

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00388 AC: 467 AN: 120324 Hom.: 0 Cov.: 21 AF XY: 0.00431 AC XY: 250 AN XY: 58066

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00376 AC: 122 AN: 32426

American (AMR) AF: 0.00672 AC: 77 AN: 11462

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 8 AN: 2946

East Asian (EAS) AF: 0.0306 AC: 89 AN: 2908

South Asian (SAS) AF: 0.00251 AC: 9 AN: 3584

European-Finnish (FIN) AF: 0.00324 AC: 24 AN: 7400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00226 AC: 129 AN: 56970

Other (OTH) AF: 0.00432 AC: 7 AN: 1620

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.110 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		-0.27

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

Other links and lift over

dbSNP: rs1778596; hg19: chr1-144991278;