Variant rs1131978 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006204.4(PDE6C):c.252G>A(p.Leu84Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,762 control chromosomes in the GnomAD database, including 26,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L84L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.19 ( 2801 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23305 hom. )

Consequence

PDE6C
NM_006204.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.499

Variant links:

Genes affected

PDE6C (HGNC:8787): (phosphodiesterase 6C) This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4). [provided by RefSeq, Mar 2010]

PDE6C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-93612977-G-A is Benign according to our data. Variant chr10-93612977-G-A is described in ClinVar as [Benign]. Clinvar id is 95346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-93612977-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.499 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6C	NM_006204.4 linkuse as main transcript	c.252G>A	p.Leu84Leu	synonymous_variant	1/22	ENST00000371447.4	NP_006195.3	P51160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4 linkuse as main transcript	c.252G>A	p.Leu84Leu	synonymous_variant	1/22	1	NM_006204.4	ENSP00000360502.3		P51160

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28325

AN:

152020

Hom.:

2792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.162

AC:

40604

AN:

250660

Hom.:

3531

AF XY:

0.164

AC XY:

22231

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.175

AC:

256456

AN:

1461624

Hom.:

23305

Cov.:

AF XY:

0.176

AC XY:

127681

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.0990

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.186

AC:

28367

AN:

152138

Hom.:

2801

Cov.:

AF XY:

0.182

AC XY:

13540

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.130

Hom.:

314

Bravo

AF:

0.194

Asia WGS

AF:

0.140

AC:

486

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 19, 2013	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2018	- -

Achromatopsia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cone dystrophy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.8

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over