rs12402521

Variant names:

• chr1-186453389-G-A
• rs12402521
• NM_002597.5:c.-24-3906C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002597.5(PDC):​c.-24-3906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,898 control chromosomes in the GnomAD database, including 9,300 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 (9300 hom., cov: 32)
• Consequence: PDC NM_002597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDC	NM_002597.5	c.-24-3906C>T		intron_variant	Intron 1 of 3	ENST00000391997.3	NP_002588.3
PDC-AS1	NR_126002.1	n.441+2115G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDC	ENST00000391997.3	c.-24-3906C>T		intron_variant	Intron 1 of 3	1	NM_002597.5	ENSP00000375855.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50547 AN: 151780 Hom.: 9257 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.333 AC: 50635 AN: 151898 Hom.: 9300 Cov.: 32 AF XY: 0.333 AC XY: 24724 AN XY: 74248

African (AFR) AF: 0.480 AC: 19884 AN: 41398

American (AMR) AF: 0.373 AC: 5697 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2197 AN: 5162

South Asian (SAS) AF: 0.256 AC: 1230 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2318 AN: 10552

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17180 AN: 67924

Other (OTH) AF: 0.348 AC: 730 AN: 2100

Alfa AF: 0.291 Hom.: 911

Bravo AF: 0.357

Asia WGS AF: 0.396 AC: 1371 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.83
PhyloP100		-1.2
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: rs12402521; hg19: chr1-186422521;