1-148960636-TTTGCCGTTTCTTCC-TTTGCCGTTTCTTCCTTGCCGTTTCTTCC

Variant names:

• chr1-148960636-T-TTTGCCGTTTCTTCC
• rs1356031674
• NM_001395426.1:c.835-16_835-3dupTGCCGTTTCTTCCT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The NM_001395426.1(PDE4DIP):​c.835-16_835-3dupTGCCGTTTCTTCCT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (573 hom., cov: 8)
  • Exomes 𝑓: 0.17 (4130 hom.)
• Consequence: PDE4DIP NM_001395426.1 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 0 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 -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.018234562 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.8, offset of 0 (no position change), new splice context is: tccttgccgtttcttcctAGccc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

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.835-16_835-3dupTGCCGTTTCTTCCT		splice_acceptor intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.1126-16_1126-3dupTGCCGTTTCTTCCT		splice_acceptor intron	N/A	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.1126-16_1126-3dupTGCCGTTTCTTCCT		splice_acceptor intron	N/A	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-18_835-17insTTGCCGTTTCTTCC		intron	N/A	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.637-18_637-17insTTGCCGTTTCTTCC		intron	N/A	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.637-18_637-17insTTGCCGTTTCTTCC		intron	N/A	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 9958 AN: 84034 Hom.: 572 Cov.: 8

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.166 AC: 45390 AN: 273124 Hom.: 4130 Cov.: 0 AF XY: 0.167 AC XY: 23232 AN XY: 139056

African (AFR) AF: 0.0443 AC: 412 AN: 9302

American (AMR) AF: 0.0892 AC: 1019 AN: 11420

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 1880 AN: 9708

East Asian (EAS) AF: 0.0150 AC: 377 AN: 25156

South Asian (SAS) AF: 0.0945 AC: 867 AN: 9170

European-Finnish (FIN) AF: 0.220 AC: 4122 AN: 18734

Middle Eastern (MID) AF: 0.151 AC: 210 AN: 1388

European-Non Finnish (NFE) AF: 0.197 AC: 33646 AN: 170506

Other (OTH) AF: 0.161 AC: 2857 AN: 17740

GnomAD4 genome AF: 0.118 AC: 9955 AN: 84078 Hom.: 573 Cov.: 8 AF XY: 0.111 AC XY: 4113 AN XY: 37188

African (AFR) AF: 0.0378 AC: 880 AN: 23306

American (AMR) AF: 0.0807 AC: 538 AN: 6670

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 374 AN: 2258

East Asian (EAS) AF: 0.0125 AC: 49 AN: 3924

South Asian (SAS) AF: 0.120 AC: 246 AN: 2044

European-Finnish (FIN) AF: 0.179 AC: 650 AN: 3636

Middle Eastern (MID) AF: 0.121 AC: 28 AN: 232

European-Non Finnish (NFE) AF: 0.173 AC: 6980 AN: 40326

Other (OTH) AF: 0.106 AC: 116 AN: 1090

Alfa AF: 0.127 Hom.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

Splicing

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

Other links and lift over

dbSNP: rs1356031674; hg19: chr1-144923853;