1-211477453-CA-C

Position:

• chr1-211477453-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001164688.2(RD3):​c.*1582delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 104,124 control chromosomes in the GnomAD database, including 2,753 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (2753 hom., cov: 26)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: RD3 NM_001164688.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.934

Genes affected

RD3 (HGNC:19689): (RD3 regulator of GUCY2D) This gene encodes a retinal protein that is associated with promyelocytic leukemia-gene product (PML) bodies in the nucleus. Mutations in this gene cause Leber congenital amaurosis type 12, a disease that results in retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RD3	NM_001164688.2	c.*1582delT		3_prime_UTR_variant	3/3	ENST00000680073.1	NP_001158160.1
RD3	NM_183059.3	c.*1582delT		3_prime_UTR_variant	3/3		NP_898882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RD3	ENST00000680073	c.*1582delT		3_prime_UTR_variant	3/3		NM_001164688.2	ENSP00000505312.1
RD3	ENST00000367002	c.*1582delT		3_prime_UTR_variant	3/3	1		ENSP00000355969.4
RD3	ENST00000484910.1	n.2138delT		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 26221 AN: 104068 Hom.: 2750 Cov.: 26

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.227

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.252 AC: 26244 AN: 104122 Hom.: 2753 Cov.: 26 AF XY: 0.257 AC XY: 12717 AN XY: 49530

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leber congenital amaurosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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: rs879756831; hg19: chr1-211650795;