chr4-653714-G-C

Variant names:

• chr4-653714-G-C
• rs28569875
• NM_000283.4:c.712-138G>C

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.712-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 982,558 control chromosomes in the GnomAD database, including 5,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1017 hom., cov: 33)
  • Exomes 𝑓: 0.096 (4237 hom.)
• Consequence: PDE6B NM_000283.4 intron
• Scores: Splicing: ADA: 0.00003223
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.413
• 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=-0.95).
• BP6: Variant 4-653714-G-C is Benign according to our data. Variant chr4-653714-G-C is described in ClinVar as Benign. ClinVar VariationId is 1241108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.712-138G>C		intron	N/A	NP_000274.3	P35913-1
	PDE6B	NM_001440547.1		c.712-138G>C		intron	N/A	NP_001427476.1
	PDE6B	NM_001145291.2		c.712-138G>C		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.712-138G>C		intron	N/A	ENSP00000420295.1	P35913-1
	PDE6B	ENST00000255622.10	TSL:1	c.712-138G>C		intron	N/A	ENSP00000255622.6	P35913-2
	PDE6B	ENST00000467152.1	TSL:1	n.110-138G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16597 AN: 152096 Hom.: 1015 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0964 AC: 80085 AN: 830344 Hom.: 4237 Cov.: 11 AF XY: 0.0957 AC XY: 41319 AN XY: 431904

African (AFR) AF: 0.134 AC: 2856 AN: 21384

American (AMR) AF: 0.0659 AC: 2458 AN: 37324

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2111 AN: 20710

East Asian (EAS) AF: 0.00222 AC: 77 AN: 34700

South Asian (SAS) AF: 0.0821 AC: 5568 AN: 67834

European-Finnish (FIN) AF: 0.135 AC: 4922 AN: 36448

Middle Eastern (MID) AF: 0.134 AC: 402 AN: 2992

European-Non Finnish (NFE) AF: 0.101 AC: 57759 AN: 569450

Other (OTH) AF: 0.0995 AC: 3932 AN: 39502

GnomAD4 genome AF: 0.109 AC: 16613 AN: 152214 Hom.: 1017 Cov.: 33 AF XY: 0.110 AC XY: 8194 AN XY: 74404

African (AFR) AF: 0.142 AC: 5913 AN: 41534

American (AMR) AF: 0.0884 AC: 1353 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.0753 AC: 363 AN: 4822

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6874 AN: 68002

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.105 Hom.: 113

Bravo AF: 0.107

Asia WGS AF: 0.0580 AC: 202 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	-0.95
CADD	Benign	4.6
DANN	Benign	0.46
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs28569875; hg19: chr4-647503;