14-21325308-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_020366.4(RPGRIP1):c.2292G>C(p.Ala764Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A764A) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
RPGRIP1
NM_020366.4 synonymous
NM_020366.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0350
Publications
2 publications found
Genes affected
RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]
RPGRIP1 Gene-Disease associations (from GenCC):
- cone-rod dystrophy 13Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- Leber congenital amaurosis 6Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- cone-rod dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP7
Synonymous conserved (PhyloP=0.035 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RPGRIP1 | NM_020366.4 | c.2292G>C | p.Ala764Ala | synonymous_variant | Exon 16 of 25 | ENST00000400017.7 | NP_065099.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RPGRIP1 | ENST00000400017.7 | c.2292G>C | p.Ala764Ala | synonymous_variant | Exon 16 of 25 | 1 | NM_020366.4 | ENSP00000382895.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152160
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
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000823 AC: 2AN: 242984 AF XY: 0.00000758 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
242984
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459114Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725596 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1459114
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
725596
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33440
American (AMR)
AF:
AC:
0
AN:
44096
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26040
East Asian (EAS)
AF:
AC:
0
AN:
39658
South Asian (SAS)
AF:
AC:
0
AN:
85816
European-Finnish (FIN)
AF:
AC:
0
AN:
53308
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1110688
Other (OTH)
AF:
AC:
0
AN:
60302
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74462 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152278
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74462
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41558
American (AMR)
AF:
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational 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
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