19-47834289-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000554.6(CRX):c.-35-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 695,998 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.036 ( 265 hom., cov: 32)
Exomes 𝑓: 0.012 ( 164 hom. )
Consequence
CRX
NM_000554.6 intron
NM_000554.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.27
Publications
0 publications found
Genes affected
CRX (HGNC:2383): (cone-rod homeobox) The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]
CRX Gene-Disease associations (from GenCC):
- 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
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 19-47834289-A-G is Benign according to our data. Variant chr19-47834289-A-G is described in ClinVar as [Benign]. Clinvar id is 1231525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRX | ENST00000221996.12 | c.-35-120A>G | intron_variant | Intron 1 of 3 | 2 | NM_000554.6 | ENSP00000221996.5 | |||
CRX | ENST00000556527.1 | n.78-1954A>G | intron_variant | Intron 1 of 1 | 1 | |||||
CRX | ENST00000566686.5 | c.-35-120A>G | intron_variant | Intron 1 of 2 | 5 | ENSP00000457808.2 | ||||
CRX | ENST00000613299.1 | c.-35-120A>G | intron_variant | Intron 1 of 2 | 3 | ENSP00000478106.1 |
Frequencies
GnomAD3 genomes AF: 0.0359 AC: 5456AN: 152180Hom.: 263 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
5456
AN:
152180
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0115 AC: 6271AN: 543700Hom.: 164 AF XY: 0.0108 AC XY: 3157AN XY: 292234 show subpopulations
GnomAD4 exome
AF:
AC:
6271
AN:
543700
Hom.:
AF XY:
AC XY:
3157
AN XY:
292234
show subpopulations
African (AFR)
AF:
AC:
1757
AN:
15736
American (AMR)
AF:
AC:
748
AN:
33976
Ashkenazi Jewish (ASJ)
AF:
AC:
107
AN:
18726
East Asian (EAS)
AF:
AC:
1617
AN:
31870
South Asian (SAS)
AF:
AC:
985
AN:
59754
European-Finnish (FIN)
AF:
AC:
66
AN:
38170
Middle Eastern (MID)
AF:
AC:
58
AN:
3964
European-Non Finnish (NFE)
AF:
AC:
455
AN:
311452
Other (OTH)
AF:
AC:
478
AN:
30052
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
320
639
959
1278
1598
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0359 AC: 5471AN: 152298Hom.: 265 Cov.: 32 AF XY: 0.0355 AC XY: 2646AN XY: 74472 show subpopulations
GnomAD4 genome
AF:
AC:
5471
AN:
152298
Hom.:
Cov.:
32
AF XY:
AC XY:
2646
AN XY:
74472
show subpopulations
African (AFR)
AF:
AC:
4599
AN:
41540
American (AMR)
AF:
AC:
346
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
22
AN:
3472
East Asian (EAS)
AF:
AC:
155
AN:
5184
South Asian (SAS)
AF:
AC:
89
AN:
4828
European-Finnish (FIN)
AF:
AC:
11
AN:
10628
Middle Eastern (MID)
AF:
AC:
5
AN:
294
European-Non Finnish (NFE)
AF:
AC:
106
AN:
68030
Other (OTH)
AF:
AC:
66
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
251
502
754
1005
1256
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
145
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Nov 10, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.