rs1409332

Variant names:

• chr10-93646057-C-A
• rs1409332
• NM_006204.4:c.1935+10C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93646057-C-A
• chr10-93646057-C-G

Variant summary

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

The NM_006204.4(PDE6C):​c.1935+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,479,756 control chromosomes in the GnomAD database, including 158,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14718 hom., cov: 32)
  • Exomes 𝑓: 0.46 (144151 hom.)
• Consequence: PDE6C NM_006204.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.15
• Publications: 9 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-93646057-C-A is Benign according to our data. Variant chr10-93646057-C-A is described in ClinVar as Benign. ClinVar VariationId is 259943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 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.1935+10C>A		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.1935+10C>A		intron	N/A	ENSP00000360502.3	P51160

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65920 AN: 151872 Hom.: 14714 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.457 AC: 114263 AN: 250124 AF XY: 0.462

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.406

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.460

GnomAD4 exome AF: 0.464 AC: 615798 AN: 1327766 Hom.: 144151 Cov.: 20 AF XY: 0.467 AC XY: 311767 AN XY: 667986

African (AFR) AF: 0.309 AC: 9601 AN: 31072

American (AMR) AF: 0.404 AC: 17981 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11180 AN: 25284

East Asian (EAS) AF: 0.430 AC: 16790 AN: 39066

South Asian (SAS) AF: 0.473 AC: 39571 AN: 83606

European-Finnish (FIN) AF: 0.538 AC: 28639 AN: 53184

Middle Eastern (MID) AF: 0.434 AC: 2385 AN: 5496

European-Non Finnish (NFE) AF: 0.469 AC: 464151 AN: 989458

Other (OTH) AF: 0.454 AC: 25500 AN: 56130

GnomAD4 genome AF: 0.434 AC: 65939 AN: 151990 Hom.: 14718 Cov.: 32 AF XY: 0.437 AC XY: 32434 AN XY: 74264

African (AFR) AF: 0.321 AC: 13304 AN: 41446

American (AMR) AF: 0.425 AC: 6487 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2113 AN: 5164

South Asian (SAS) AF: 0.473 AC: 2277 AN: 4810

European-Finnish (FIN) AF: 0.554 AC: 5853 AN: 10568

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32906 AN: 67958

Other (OTH) AF: 0.417 AC: 880 AN: 2112

Alfa AF: 0.462 Hom.: 14067

Bravo AF: 0.416

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Cone dystrophy 4 (2)
-	-	1	Achromatopsia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1409332; hg19: chr10-95405814; COSMIC: COSV65116662;