rs714549

chr10-93629326-A-Gchr10-93629326-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.251

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE6C	NM_006204.4	c.1119+21A>G		intron_variant		ENST00000371447.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE6C	ENST00000371447.4	c.1119+21A>G		intron_variant		1	NM_006204.4	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56080 AN: 151858 Hom.: 10560 Cov.: 32

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

GnomAD3 exomes AF: 0.355 AC: 89142 AN: 251204 Hom.: 16352 AF XY: 0.349 AC XY: 47347 AN XY: 135774

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 SAS exome AF: 0.308

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.: 26 AF XY: 0.333 AC XY: 234598 AN XY: 704372

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.369 AC: 56152 AN: 151976 Hom.: 10582 Cov.: 32 AF XY: 0.368 AC XY: 27360 AN XY: 74290

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.352

Alfa AF: 0.346 Hom.: 2043

Bravo AF: 0.379

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.0
Dann	Benign	0.66

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: rs714549; hg19: chr10-95389083; COSMIC: COSV65116901;