chr1-148962551-C-T

Variant names:

• chr1-148962551-C-T
• rs71664015
• NM_001395426.1:c.1303C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PP3_Moderate BP6_Very_Strong BP7

The NM_001395426.1(PDE4DIP):​c.1303C>T​(p.Leu435Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PDE4DIP NM_001395426.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58
• Publications: 12 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: Benign. The variant received -7 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.33
• BP6: Variant 1-148962551-C-T is Benign according to our data. Variant chr1-148962551-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 769527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	NM_001395426.1	MANE Select	c.1303C>T	p.Leu435Leu	synonymous	Exon 12 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.1594C>T	p.Leu532Leu	synonymous	Exon 5 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.1594C>T	p.Leu532Leu	synonymous	Exon 5 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.1303C>T	p.Leu435Leu	synonymous	Exon 12 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.1105C>T	p.Leu369Leu	synonymous	Exon 9 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.1105C>T	p.Leu369Leu	synonymous	Exon 9 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD2 exomes AF: 0.187 AC: 45152 AN: 240946 AF XY: 0.185

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.00000196 AC: 1 AN: 510188 Hom.: 0 Cov.: 5 AF XY: 0.00000368 AC XY: 1 AN XY: 272004

African (AFR) AF: 0.00 AC: 0 AN: 14644

American (AMR) AF: 0.00 AC: 0 AN: 26106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15864

East Asian (EAS) AF: 0.00 AC: 0 AN: 33646

South Asian (SAS) AF: 0.00 AC: 0 AN: 53266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2682

European-Non Finnish (NFE) AF: 0.00000332 AC: 1 AN: 301302

Other (OTH) AF: 0.00 AC: 0 AN: 28604

GnomAD4 genome Cov.: 16

Alfa AF: 0.157 Hom.: 892

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		1.6
Mutation Taster		=93/7	polymorphism

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: rs71664015; hg19: chr1-144921924; COSMIC: COSV57684451; COSMIC: COSV57684451;