1-186444582-G-C

Position:

• chr1-186444582-G-C

Variant summary

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

The NM_002597.5(PDC):​c.214-76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 941,664 control chromosomes in the GnomAD database, including 11,256 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 0.13 (1577 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9679 hom.)
• Consequence: PDC NM_002597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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:40432): (PDC antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDC	NM_002597.5	c.214-76C>G		intron_variant		ENST00000391997.3
PDC-AS1	NR_126002.1	n.346-6597G>C		intron_variant, non_coding_transcript_variant
PDC	NM_022576.4	c.58-76C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDC	ENST00000391997.3	c.214-76C>G		intron_variant		1	NM_002597.5	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19484 AN: 151908 Hom.: 1568 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.138 AC: 109351 AN: 789638 Hom.: 9679 AF XY: 0.137 AC XY: 55539 AN XY: 404006

Gnomad4 AFR exome AF: 0.0599

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.0928

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.128 AC: 19507 AN: 152026 Hom.: 1577 Cov.: 32 AF XY: 0.134 AC XY: 9955 AN XY: 74310

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0463 Hom.: 44

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11812050; hg19: chr1-186413714;