rs1465831

chr2-177704346-G-T

Variant summary

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

The NM_016953.4(PDE11A):c.2154-3135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 151,898 control chromosomes in the GnomAD database, including 1,905 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 0.094 (1905 hom., cov: 31)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.2154-3135C>A		intron_variant		ENST00000286063.11
PDE11A-AS1	NR_136171.1	n.644+1597G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.2154-3135C>A		intron_variant		1	NM_016953.4	P1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14233 AN: 151780 Hom.: 1898 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0939 AC: 14266 AN: 151898 Hom.: 1905 Cov.: 31 AF XY: 0.0913 AC XY: 6779 AN XY: 74282

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00603

Gnomad4 FIN AF: 0.0168

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0651

Alfa AF: 0.0675 Hom.: 166

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.31
Dann	Benign	0.21

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: rs1465831; hg19: chr2-178569074;