dbSNP rs714549: PDE6C:c.1119+21A>G (chr10-93629326-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006204.4(PDE6C):c.1119+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,561,552 control chromosomes in the GnomAD database, including 90,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10582 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79992 hom. )

Consequence

PDE6C
NM_006204.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.251

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

cone dystrophy 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
PDE6C-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PDE6C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-93629326-A-G is Benign according to our data. Variant chr10-93629326-A-G is described in ClinVar as Benign. ClinVar VariationId is 259939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006204.4. 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
	PDE6C	NM_006204.4	MANE Select	c.1119+21A>G		intron	N/A	NP_006195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	ENST00000371447.4	TSL:1 MANE Select	c.1119+21A>G		intron	N/A	ENSP00000360502.3	P51160

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56080

AN:

151858

Hom.:

10560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.355

AC:

89142

AN:

251204

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.333

AC:

469567

AN:

1409576

Hom.:

79992

Cov.:

AF XY:

0.333

AC XY:

234598

AN XY:

704372

show subpopulations

African (AFR)

AF:

0.422

AC:

13612

AN:

32238

American (AMR)

AF:

0.398

AC:

17787

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

8354

AN:

25794

East Asian (EAS)

AF:

0.465

AC:

18289

AN:

39352

South Asian (SAS)

AF:

0.308

AC:

26210

AN:

85224

European-Finnish (FIN)

AF:

0.330

AC:

17611

AN:

53354

Middle Eastern (MID)

AF:

0.331

AC:

1877

AN:

5678

European-Non Finnish (NFE)

AF:

0.324

AC:

345444

AN:

1064806

Other (OTH)

AF:

0.348

AC:

20383

AN:

58494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

15317

30635

45952

61270

76587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11050

22100

33150

44200

55250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.369

AC:

56152

AN:

151976

Hom.:

10582

Cov.:

AF XY:

0.368

AC XY:

27360

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.429

AC:

17795

AN:

41432

American (AMR)

AF:

0.388

AC:

5934

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1096

AN:

3466

East Asian (EAS)

AF:

0.466

AC:

2404

AN:

5158

South Asian (SAS)

AF:

0.306

AC:

1472

AN:

4818

European-Finnish (FIN)

AF:

0.326

AC:

3449

AN:

10582

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.335

AC:

22776

AN:

67934

Other (OTH)

AF:

0.352

AC:

743

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1838

3676

5514

7352

9190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.347

Hom.:

2105

Bravo

AF:

0.379

Asia WGS

AF:

0.409

AC:

1422

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

(source)

DANN

Benign

0.66

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over