rs2785137

chr10-93626450-G-Achr10-93626450-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006204.4(PDE6C):c.940-190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,024 control chromosomes in the GnomAD database, including 10,468 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10468 hom., cov: 32)
• Consequence: PDE6C NM_006204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE6C	NM_006204.4	c.940-190G>A		intron_variant		ENST00000371447.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6C	ENST00000371447.4	c.940-190G>A		intron_variant		1	NM_006204.4	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55751 AN: 151906 Hom.: 10447 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55821 AN: 152024 Hom.: 10468 Cov.: 32 AF XY: 0.366 AC XY: 27209 AN XY: 74318

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.351

Alfa AF: 0.338 Hom.: 8350

Bravo AF: 0.377

Asia WGS AF: 0.407 AC: 1414 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.0
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs2785137; hg19: chr10-95386207;