rs1698683

Variant names:

• chr1-148967799-G-A
• rs1698683
• NM_001395426.1:c.1877G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-148967799-G-A
• chr1-148967799-G-C
• chr1-148967799-G-T

Variant summary

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

The NM_001395426.1(PDE4DIP):​c.1877G>A​(p.Trp626*) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.59
• Publications: 29 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 1-148967799-G-A is Benign according to our data. Variant chr1-148967799-G-A is described in ClinVar as Benign. ClinVar VariationId is 2791670.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.1877G>A	p.Trp626*	stop_gained	Exon 16 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.2168G>A	p.Trp723*	stop_gained	Exon 9 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.2168G>A	p.Trp723*	stop_gained	Exon 9 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000695795.1	MANE Select	c.1877G>A	p.Trp626*	stop_gained	Exon 16 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.1679G>A	p.Trp560*	stop_gained	Exon 13 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.1679G>A	p.Trp560*	stop_gained	Exon 13 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 1649 AN: 108500 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00522

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00987

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00667

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0521

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.256 AC: 55124 AN: 215208 AF XY: 0.257

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.0301

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.273

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00777 AC: 6709 AN: 862984 Hom.: 0 Cov.: 14 AF XY: 0.00715 AC XY: 3218 AN XY: 450378

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

African (AFR) AF: 0.00729 AC: 147 AN: 20156

American (AMR) AF: 0.000310 AC: 13 AN: 41996

Ashkenazi Jewish (ASJ) AF: 0.00296 AC: 59 AN: 19964

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37584

South Asian (SAS) AF: 0.000897 AC: 67 AN: 74710

European-Finnish (FIN) AF: 0.00111 AC: 53 AN: 47744

Middle Eastern (MID) AF: 0.00283 AC: 12 AN: 4242

European-Non Finnish (NFE) AF: 0.0105 AC: 6092 AN: 578014

Other (OTH) AF: 0.00687 AC: 265 AN: 38574

⚠️ 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: 0.0152 AC: 1653 AN: 108578 Hom.: 0 Cov.: 27 AF XY: 0.0152 AC XY: 819 AN XY: 53774

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

African (AFR) AF: 0.0213 AC: 570 AN: 26752

American (AMR) AF: 0.0105 AC: 123 AN: 11708

Ashkenazi Jewish (ASJ) AF: 0.00987 AC: 25 AN: 2532

East Asian (EAS) AF: 0.000396 AC: 2 AN: 5048

South Asian (SAS) AF: 0.00692 AC: 27 AN: 3904

European-Finnish (FIN) AF: 0.0262 AC: 195 AN: 7452

Middle Eastern (MID) AF: 0.0568 AC: 10 AN: 176

European-Non Finnish (NFE) AF: 0.0139 AC: 680 AN: 48758

Other (OTH) AF: 0.0115 AC: 17 AN: 1482

⚠️ 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: 0.340 Hom.: 2943

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	38
DANN	Uncertain	1.0
PhyloP100		5.6
Vest4		0.37

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: rs1698683; hg19: chr1-144916676; COSMIC: COSV57717521; COSMIC: COSV57717521;