rs11187564

Variant names:

• chr10-93635488-C-T
• rs11187564
• NM_006204.4:c.1270-9C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-93635488-C-T
• chr10-93635488-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.1270-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,606,120 control chromosomes in the GnomAD database, including 3,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (272 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3680 hom.)
• Consequence: PDE6C NM_006204.4 intron
• Scores: Splicing: ADA: 0.00001187
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.111
• Publications: 7 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=-0.84).
• BP6: Variant 10-93635488-C-T is Benign according to our data. Variant chr10-93635488-C-T is described in ClinVar as Benign. ClinVar VariationId is 259941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 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.1270-9C>T		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.1270-9C>T		intron	N/A	ENSP00000360502.3	P51160

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8264 AN: 152066 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0526

GnomAD2 exomes AF: 0.0615 AC: 15435 AN: 251128 AF XY: 0.0632

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.0467

Gnomad ASJ exome AF: 0.0478

Gnomad EAS exome AF: 0.0671

Gnomad FIN exome AF: 0.0627

Gnomad NFE exome AF: 0.0697

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0687 AC: 99831 AN: 1453936 Hom.: 3680 Cov.: 27 AF XY: 0.0695 AC XY: 50275 AN XY: 723858

African (AFR) AF: 0.0102 AC: 340 AN: 33394

American (AMR) AF: 0.0489 AC: 2185 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 1268 AN: 26070

East Asian (EAS) AF: 0.0647 AC: 2563 AN: 39640

South Asian (SAS) AF: 0.0704 AC: 6058 AN: 86028

European-Finnish (FIN) AF: 0.0625 AC: 3335 AN: 53348

Middle Eastern (MID) AF: 0.0660 AC: 379 AN: 5746

European-Non Finnish (NFE) AF: 0.0720 AC: 79603 AN: 1104884

Other (OTH) AF: 0.0682 AC: 4100 AN: 60118

GnomAD4 genome AF: 0.0543 AC: 8263 AN: 152184 Hom.: 272 Cov.: 32 AF XY: 0.0542 AC XY: 4030 AN XY: 74400

African (AFR) AF: 0.0141 AC: 586 AN: 41538

American (AMR) AF: 0.0595 AC: 909 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5180

South Asian (SAS) AF: 0.0632 AC: 304 AN: 4812

European-Finnish (FIN) AF: 0.0570 AC: 604 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5078 AN: 67994

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0620 Hom.: 238

Bravo AF: 0.0515

Asia WGS AF: 0.0670 AC: 235 AN: 3476

EpiCase AF: 0.0695

EpiControl AF: 0.0678

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0020
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: rs11187564; hg19: chr10-95395245; COSMIC: COSV65114745;