rs3770018

Variant names:

• chr2-177676076-A-C
• rs3770018
• NM_016953.4:c.2424-558T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016953.4. 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
	PDE11A	NM_016953.4	MANE Select	c.2424-558T>G		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.1674-558T>G		intron	N/A	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.1350-558T>G		intron	N/A	NP_001070826.1	Q9HCR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	ENST00000286063.11	TSL:1 MANE Select	c.2424-558T>G		intron	N/A	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.1674-558T>G		intron	N/A	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.1350-558T>G		intron	N/A	ENSP00000386539.1	Q9HCR9-3

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

African (AFR) AF: 0.564 AC: 461 AN: 818

American (AMR) AF: 0.107 AC: 377 AN: 3530

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 96 AN: 750

East Asian (EAS) AF: 0.195 AC: 563 AN: 2894

South Asian (SAS) AF: 0.201 AC: 1106 AN: 5512

European-Finnish (FIN) AF: 0.0575 AC: 69 AN: 1200

Middle Eastern (MID) AF: 0.177 AC: 22 AN: 124

European-Non Finnish (NFE) AF: 0.0906 AC: 2125 AN: 23452

Other (OTH) AF: 0.121 AC: 227 AN: 1874

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

African (AFR) AF: 0.578 AC: 23965 AN: 41440

American (AMR) AF: 0.136 AC: 2077 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5166

South Asian (SAS) AF: 0.206 AC: 994 AN: 4820

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10606

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7126 AN: 68006

Other (OTH) AF: 0.221 AC: 464 AN: 2102

Alfa AF: 0.211 Hom.: 1988

Bravo AF: 0.264

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.73
PhyloP100		0.41
PromoterAI		0.00090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3770018; hg19: chr2-178540804;