rs3770018

Positions:

• chr2-177676076-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(PDE11A):​c.2424-558T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 192,254 control chromosomes in the GnomAD database, including 8,428 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (7935 hom., cov: 33)
  • Exomes 𝑓: 0.13 (493 hom.)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

Genes affected

PDE11A (HGNC:8773): (phosphodiesterase 11A) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PDE11A-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.2424-558T>G		intron_variant		ENST00000286063.11
PDE11A-AS1	NR_136171.1	n.104+2651A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.2424-558T>G		intron_variant		1	NM_016953.4	P1
PDE11A-AS1	ENST00000653062.1	n.365+22293A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36945 AN: 151982 Hom.: 7919 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.126 AC: 5046 AN: 40154 Hom.: 493 Cov.: 0 AF XY: 0.132 AC XY: 2829 AN XY: 21404

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0906

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.243 AC: 37007 AN: 152100 Hom.: 7935 Cov.: 33 AF XY: 0.238 AC XY: 17701 AN XY: 74382

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.221

Alfa AF: 0.177 Hom.: 783

Bravo AF: 0.264

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs3770018; hg19: chr2-178540804;