rs30825

Positions:

• chr5-149913497-G-A
• chr5-149913497-G-C

Variant summary

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

The NM_000440.3(PDE6A):​c.998+1446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,944 control chromosomes in the GnomAD database, including 29,433 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 0.62 (29433 hom., cov: 31)
• Consequence: PDE6A NM_000440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

PDE6A (HGNC:8785): (phosphodiesterase 6A) This gene encodes the cyclic-GMP (cGMP)-specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits. cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and guanylate cyclase cGMP synthesis. The protein is a subunit of a key phototransduction enzyme and participates in processes of transmission and amplification of the visual signal. Mutations in this gene have been identified as one cause of autosomal recessive retinitis pigmentosa. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE6A	NM_000440.3	c.998+1446C>T		intron_variant		ENST00000255266.10
PDE6A	NM_001410788.1	c.755+1446C>T		intron_variant
PDE6A	XM_011537650.3	c.113+1446C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6A	ENST00000255266.10	c.998+1446C>T		intron_variant		1	NM_000440.3	P1
PDE6A	ENST00000508173.5	n.1118+1446C>T		intron_variant, non_coding_transcript_variant		1
PDE6A	ENST00000613228.1	c.755+1446C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93584 AN: 151824 Hom.: 29424 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.616 AC: 93634 AN: 151944 Hom.: 29433 Cov.: 31 AF XY: 0.615 AC XY: 45688 AN XY: 74248

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.633

Alfa AF: 0.667 Hom.: 69388

Bravo AF: 0.608

Asia WGS AF: 0.501 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.54

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: rs30825; hg19: chr5-149293060;