4-653717-A-G

Variant names:

• chr4-653717-A-G
• rs9992641
• NM_000283.4:c.712-135A>G

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.712-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 997,264 control chromosomes in the GnomAD database, including 11,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3422 hom., cov: 33)
  • Exomes 𝑓: 0.13 (8178 hom.)
• Consequence: PDE6B NM_000283.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.14
• Publications: 5 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=-0.97).
• BP6: Variant 4-653717-A-G is Benign according to our data. Variant chr4-653717-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 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.712-135A>G		intron	N/A	NP_000274.3	P35913-1
	PDE6B	NM_001440547.1		c.712-135A>G		intron	N/A	NP_001427476.1
	PDE6B	NM_001145291.2		c.712-135A>G		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.712-135A>G		intron	N/A	ENSP00000420295.1	P35913-1
	PDE6B	ENST00000255622.10	TSL:1	c.712-135A>G		intron	N/A	ENSP00000255622.6	P35913-2
	PDE6B	ENST00000467152.1	TSL:1	n.110-135A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28050 AN: 152030 Hom.: 3391 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.129 AC: 108789 AN: 845116 Hom.: 8178 Cov.: 11 AF XY: 0.127 AC XY: 55682 AN XY: 439540

African (AFR) AF: 0.336 AC: 7269 AN: 21642

American (AMR) AF: 0.0872 AC: 3312 AN: 37982

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 2943 AN: 20974

East Asian (EAS) AF: 0.00243 AC: 85 AN: 35004

South Asian (SAS) AF: 0.100 AC: 6902 AN: 68882

European-Finnish (FIN) AF: 0.151 AC: 5592 AN: 37156

Middle Eastern (MID) AF: 0.172 AC: 525 AN: 3046

European-Non Finnish (NFE) AF: 0.132 AC: 76660 AN: 580488

Other (OTH) AF: 0.138 AC: 5501 AN: 39942

GnomAD4 genome AF: 0.185 AC: 28119 AN: 152148 Hom.: 3422 Cov.: 33 AF XY: 0.182 AC XY: 13545 AN XY: 74384

African (AFR) AF: 0.341 AC: 14137 AN: 41486

American (AMR) AF: 0.126 AC: 1926 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1559 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8998 AN: 67984

Other (OTH) AF: 0.159 AC: 336 AN: 2116

Alfa AF: 0.0558 Hom.: 60

Bravo AF: 0.191

Asia WGS AF: 0.0810 AC: 283 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	-0.97
CADD	Benign	0.63
DANN	Benign	0.48
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9992641; hg19: chr4-647506; COSMIC: COSV55329276; COSMIC: COSV55329276;