1-186444582-G-C

Variant names:

• chr1-186444582-G-C
• rs11812050
• NM_002597.5:c.214-76C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002597.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDC	NM_002597.5	MANE Select	c.214-76C>G		intron	N/A	NP_002588.3
	PDC	NM_022576.4		c.58-76C>G		intron	N/A	NP_072098.1
	PDC-AS1	NR_126002.1		n.346-6597G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDC	ENST00000391997.3	TSL:1 MANE Select	c.214-76C>G		intron	N/A	ENSP00000375855.2
	PDC	ENST00000497198.1	TSL:1	c.58-76C>G		intron	N/A	ENSP00000422775.1
	PDC-AS1	ENST00000622121.1	TSL:4	n.346-6597G>C		intron	N/A

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

African (AFR) AF: 0.0599 AC: 1135 AN: 18950

American (AMR) AF: 0.258 AC: 6111 AN: 23672

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 1558 AN: 16788

East Asian (EAS) AF: 0.400 AC: 13434 AN: 33562

South Asian (SAS) AF: 0.128 AC: 7046 AN: 54836

European-Finnish (FIN) AF: 0.145 AC: 4932 AN: 34014

Middle Eastern (MID) AF: 0.0650 AC: 267 AN: 4110

European-Non Finnish (NFE) AF: 0.123 AC: 69711 AN: 566282

Other (OTH) AF: 0.138 AC: 5157 AN: 37424

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

African (AFR) AF: 0.0637 AC: 2645 AN: 41492

American (AMR) AF: 0.216 AC: 3290 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1960 AN: 5158

South Asian (SAS) AF: 0.138 AC: 663 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1590 AN: 10564

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8490 AN: 67944

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.0463 Hom.: 44

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11812050; hg19: chr1-186413714;