chr1-148960744-GA-G

Variant names:

• chr1-148960744-GA-G
• rs3215779
• NM_001395426.1:c.927delA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001395426.1(PDE4DIP):​c.927delA​(p.Glu309AspfsTer23) variant causes a frameshift change. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.95
• Publications: 25 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 -2 ACMG points.

• BP6: Variant 1-148960744-GA-G is Benign according to our data. Variant chr1-148960744-GA-G is described in ClinVar as Benign. ClinVar VariationId is 403294.Status of the report is criteria_provided_single_submitter, 1 stars.

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.927delA	p.Glu309AspfsTer23	frameshift	Exon 9 of 47	NP_001382355.1
	PDE4DIP	NM_001395297.1		c.1218delA	p.Glu406AspfsTer23	frameshift	Exon 2 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.1218delA	p.Glu406AspfsTer23	frameshift	Exon 2 of 40	NP_001337449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000695795.1	MANE Select	c.927delA	p.Glu309AspfsTer23	frameshift	Exon 9 of 47	ENSP00000512175.1
	PDE4DIP	ENST00000369356.8	TSL:1	c.729delA	p.Glu243AspfsTer23	frameshift	Exon 6 of 44	ENSP00000358363.4
	PDE4DIP	ENST00000369354.7	TSL:1	c.729delA	p.Glu243AspfsTer23	frameshift	Exon 6 of 44	ENSP00000358360.3

Frequencies

GnomAD3 genomes AF: 0.000450 AC: 55 AN: 122224 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0000608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.000952

Gnomad FIN AF: 0.000389

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000501

Gnomad OTH AF: 0.000650

GnomAD2 exomes AF: 0.173 AC: 40004 AN: 231748 AF XY: 0.171

Gnomad AFR exome AF: 0.0296

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00583 AC: 2330 AN: 399700 Hom.: 0 Cov.: 4 AF XY: 0.00594 AC XY: 1239 AN XY: 208416

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

African (AFR) AF: 0.000252 AC: 3 AN: 11888

American (AMR) AF: 0.0115 AC: 195 AN: 16918

Ashkenazi Jewish (ASJ) AF: 0.00154 AC: 19 AN: 12350

East Asian (EAS) AF: 0.0120 AC: 356 AN: 29626

South Asian (SAS) AF: 0.0118 AC: 354 AN: 29878

European-Finnish (FIN) AF: 0.00434 AC: 129 AN: 29712

Middle Eastern (MID) AF: 0.00164 AC: 3 AN: 1830

European-Non Finnish (NFE) AF: 0.00480 AC: 1169 AN: 243750

Other (OTH) AF: 0.00430 AC: 102 AN: 23748

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000441 AC: 54 AN: 122338 Hom.: 0 Cov.: 17 AF XY: 0.000534 AC XY: 31 AN XY: 58046

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

African (AFR) AF: 0.0000606 AC: 2 AN: 33020

American (AMR) AF: 0.000360 AC: 4 AN: 11098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3106

East Asian (EAS) AF: 0.00347 AC: 13 AN: 3748

South Asian (SAS) AF: 0.000635 AC: 2 AN: 3148

European-Finnish (FIN) AF: 0.000389 AC: 3 AN: 7714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000501 AC: 29 AN: 57868

Other (OTH) AF: 0.000643 AC: 1 AN: 1556

⚠️ 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: 0.0240 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9
Mutation Taster		=8/192	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3215779; hg19: chr1-144923731; COSMIC: COSV57675994; COSMIC: COSV57675994;