1-186448565-T-C

Position:

• chr1-186448565-T-C

Variant summary

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

The NM_002597.5(PDC):​c.61+834A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 283,448 control chromosomes in the GnomAD database, including 13,989 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 0.33 (9301 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4688 hom.)
• Consequence: PDC NM_002597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

PDC (HGNC:8759): (phosducin) This gene encodes a phosphoprotein, which is located in the outer and inner segments of the rod cells in the retina. This protein may participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism. It modulates the phototransduction cascade by interacting with the beta and gamma subunits of the retinal G-protein transducin. This gene is a potential candidate gene for retinitis pigmentosa and Usher syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PDC-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDC	NM_002597.5	c.61+834A>G		intron_variant		ENST00000391997.3	NP_002588.3
PDC	NM_022576.4	c.-96+63A>G		intron_variant			NP_072098.1
PDC-AS1	NR_126002.1	n.346-2614T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDC	ENST00000391997.3	c.61+834A>G		intron_variant		1	NM_002597.5	ENSP00000375855.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50533 AN: 151826 Hom.: 9258 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.263 AC: 34542 AN: 131502 Hom.: 4688 AF XY: 0.262 AC XY: 16671 AN XY: 63700

Gnomad4 AFR exome AF: 0.507

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.333 AC: 50622 AN: 151946 Hom.: 9301 Cov.: 32 AF XY: 0.333 AC XY: 24722 AN XY: 74298

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.348

Alfa AF: 0.185 Hom.: 482

Bravo AF: 0.358

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.42

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: rs6672836; hg19: chr1-186417697;