rs1553114

Variant names:

• chr5-58990798-C-T
• rs1553114
• NM_001104631.2:c.1287+6G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-58990798-C-T
• chr5-58990798-C-A
• chr5-58990798-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001104631.2(PDE4D):​c.1287+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,467,162 control chromosomes in the GnomAD database, including 515,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50820 hom., cov: 30)
  • Exomes 𝑓: 0.84 (465100 hom.)
• Consequence: PDE4D NM_001104631.2 splice_region, intron
• Scores: Splicing: ADA: 0.00009314
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0420
• Publications: 15 publications found

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D Gene-Disease associations (from GenCC):

• acrodysostosis 2 with or without hormone resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• acrodysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrodysostosis with multiple hormone resistance

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chromosome 5q12 deletion syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-58990798-C-T is Benign according to our data. Variant chr5-58990798-C-T is described in ClinVar as Benign. ClinVar VariationId is 353992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104631.2. 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
	PDE4D	NM_001104631.2	MANE Select	c.1287+6G>A		splice_region intron	N/A	NP_001098101.1	A0A140VJR0
	PDE4D	NM_001165899.2		c.1104+6G>A		splice_region intron	N/A	NP_001159371.1	Q08499-11
	PDE4D	NM_001364599.1		c.1104+6G>A		splice_region intron	N/A	NP_001351528.1	Q08499-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.1287+6G>A		splice_region intron	N/A	ENSP00000345502.6	Q08499-1
	PDE4D	ENST00000502484.6	TSL:1	c.1104+6G>A		splice_region intron	N/A	ENSP00000423094.2	Q08499-11
	PDE4D	ENST00000507116.6	TSL:1	c.1095+6G>A		splice_region intron	N/A	ENSP00000424852.1	Q08499-6

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124007 AN: 151818 Hom.: 50790 Cov.: 30

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.816

GnomAD2 exomes AF: 0.838 AC: 173259 AN: 206700 AF XY: 0.835

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.919

Gnomad ASJ exome AF: 0.821

Gnomad EAS exome AF: 0.853

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.837

Gnomad OTH exome AF: 0.841

GnomAD4 exome AF: 0.840 AC: 1104911 AN: 1315228 Hom.: 465100 Cov.: 19 AF XY: 0.838 AC XY: 551544 AN XY: 658034

African (AFR) AF: 0.734 AC: 22540 AN: 30694

American (AMR) AF: 0.914 AC: 37250 AN: 40742

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 20415 AN: 24914

East Asian (EAS) AF: 0.843 AC: 32189 AN: 38192

South Asian (SAS) AF: 0.800 AC: 63025 AN: 78784

European-Finnish (FIN) AF: 0.831 AC: 42809 AN: 51512

Middle Eastern (MID) AF: 0.784 AC: 4329 AN: 5520

European-Non Finnish (NFE) AF: 0.845 AC: 835889 AN: 989512

Other (OTH) AF: 0.839 AC: 46465 AN: 55358

GnomAD4 genome AF: 0.817 AC: 124084 AN: 151934 Hom.: 50820 Cov.: 30 AF XY: 0.818 AC XY: 60723 AN XY: 74242

African (AFR) AF: 0.746 AC: 30869 AN: 41406

American (AMR) AF: 0.881 AC: 13446 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2803 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4355 AN: 5158

South Asian (SAS) AF: 0.805 AC: 3876 AN: 4812

European-Finnish (FIN) AF: 0.828 AC: 8714 AN: 10530

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57259 AN: 67978

Other (OTH) AF: 0.819 AC: 1729 AN: 2112

Alfa AF: 0.834 Hom.: 199622

Bravo AF: 0.819

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Acrodysostosis 2 with or without hormone resistance (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		0.042
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.0
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: rs1553114; hg19: chr5-58286625;