chr4-653813-G-A

Variant names:

• chr4-653813-G-A
• rs28514424
• NM_000283.4:c.712-39G>A

Variant summary

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

The NM_000283.4(PDE6B):​c.712-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,611,514 control chromosomes in the GnomAD database, including 573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (303 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (270 hom.)
• Consequence: PDE6B NM_000283.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516
• Publications: 1 publications found

Genes affected

PDE6B (HGNC:8786): (phosphodiesterase 6B) Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

PDE6B-AS1 (HGNC:40438): (PDE6B antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-653813-G-A is Benign according to our data. Variant chr4-653813-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000283.4. 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
	PDE6B	NM_000283.4	MANE Select	c.712-39G>A		intron	N/A	NP_000274.3	P35913-1
	PDE6B	NM_001440547.1		c.712-39G>A		intron	N/A	NP_001427476.1
	PDE6B	NM_001145291.2		c.712-39G>A		intron	N/A	NP_001138763.2	P35913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6B	ENST00000496514.6	TSL:1 MANE Select	c.712-39G>A		intron	N/A	ENSP00000420295.1	P35913-1
	PDE6B	ENST00000255622.10	TSL:1	c.712-39G>A		intron	N/A	ENSP00000255622.6	P35913-2
	PDE6B-AS1	ENST00000468356.3	TSL:1	n.1440C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5342 AN: 152176 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.0282

GnomAD2 exomes AF: 0.0112 AC: 2799 AN: 249536 AF XY: 0.00886

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.00903

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00285

Gnomad OTH exome AF: 0.00987

GnomAD4 exome AF: 0.00587 AC: 8561 AN: 1459220 Hom.: 270 Cov.: 31 AF XY: 0.00548 AC XY: 3981 AN XY: 726100

African (AFR) AF: 0.118 AC: 3939 AN: 33422

American (AMR) AF: 0.00982 AC: 439 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00702 AC: 605 AN: 86230

European-Finnish (FIN) AF: 0.00149 AC: 78 AN: 52450

Middle Eastern (MID) AF: 0.0166 AC: 95 AN: 5730

European-Non Finnish (NFE) AF: 0.00242 AC: 2683 AN: 1110542

Other (OTH) AF: 0.0118 AC: 714 AN: 60316

GnomAD4 genome AF: 0.0352 AC: 5362 AN: 152294 Hom.: 303 Cov.: 33 AF XY: 0.0334 AC XY: 2490 AN XY: 74474

African (AFR) AF: 0.117 AC: 4842 AN: 41532

American (AMR) AF: 0.0142 AC: 217 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00281 AC: 191 AN: 68042

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0168 Hom.: 34

Bravo AF: 0.0399

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.75
DANN	Benign	0.84
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28514424; hg19: chr4-647602;