19-47834486-G-C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000554.6(CRX):c.43G>C(p.Ala15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A15T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000554.6 missense
Scores
Clinical Significance
Conservation
Publications
- cone-rod dystrophy 2Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
- hereditary macular dystrophyInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Leber congenital amaurosis 7Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- cone-rod dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRX | ENST00000221996.12 | c.43G>C | p.Ala15Pro | missense_variant | Exon 2 of 4 | 2 | NM_000554.6 | ENSP00000221996.5 | ||
CRX | ENST00000556527.1 | n.78-1757G>C | intron_variant | Intron 1 of 1 | 1 | |||||
CRX | ENST00000566686.5 | c.43G>C | p.Ala15Pro | missense_variant | Exon 2 of 3 | 5 | ENSP00000457808.2 | |||
CRX | ENST00000613299.1 | c.43G>C | p.Ala15Pro | missense_variant | Exon 2 of 3 | 3 | ENSP00000478106.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 show subpopulations
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727246 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298 show subpopulations
ClinVar
Submissions by phenotype
Leber congenital amaurosis 7;C3489532:Cone-rod dystrophy 2 Uncertain:1
This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 15 of the CRX protein (p.Ala15Pro). This variant has not been reported in the literature in individuals affected with CRX-related conditions. ClinVar contains an entry for this variant (Variation ID: 867204). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CRX protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Retinal dystrophy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at