rs714549

Variant names:

• chr10-93629326-A-G
• rs714549
• NM_006204.4:c.1119+21A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-93629326-A-G
• chr10-93629326-A-T

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.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:3
• Conservation: PhyloP100: -0.251
• Publications: 10 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
• inherited retinal dystrophy

  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=-0.89).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4	c.1119+21A>G		intron_variant	Intron 8 of 21	ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4	c.1119+21A>G		intron_variant	Intron 8 of 21	1	NM_006204.4	ENSP00000360502.3

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

GnomAD2 exomes AF: 0.355 AC: 89142 AN: 251204 AF XY: 0.349

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

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

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

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: 94 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22776 AN: 67934

Other (OTH) AF: 0.352 AC: 743 AN: 2108

Alfa AF: 0.347 Hom.: 2105

Bravo AF: 0.379

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.66
PhyloP100		-0.25
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: rs714549; hg19: chr10-95389083; COSMIC: COSV65116901;