3-33114497-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_006371.5(CRTAP):c.420G>T(p.Ala140Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,414 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A140A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CRTAP
NM_006371.5 synonymous
NM_006371.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.97
Publications
0 publications found
Genes affected
CRTAP (HGNC:2379): (cartilage associated protein) The protein encoded by this gene is similar to the chicken and mouse CRTAP genes. The encoded protein is a scaffolding protein that may influence the activity of at least one member of the cytohesin/ARNO family in response to specific cellular stimuli. Defects in this gene are associated with osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility and low bone mass. [provided by RefSeq, Jul 2008]
CRTAP Gene-Disease associations (from GenCC):
- osteogenesis imperfecta type 7Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- osteogenesis imperfecta type 2Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 3Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 4Inheritance: 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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 3-33114497-G-T is Benign according to our data. Variant chr3-33114497-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 465809.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.97 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CRTAP | NM_006371.5 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 7 | ENST00000320954.11 | NP_006362.1 | |
| CRTAP | NM_001393363.1 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 6 | NP_001380292.1 | ||
| CRTAP | NM_001393364.1 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 6 | NP_001380293.1 | ||
| CRTAP | NM_001393365.1 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 6 | NP_001380294.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CRTAP | ENST00000320954.11 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 7 | 1 | NM_006371.5 | ENSP00000323696.5 | ||
| CRTAP | ENST00000449224.1 | c.420G>T | p.Ala140Ala | synonymous_variant | Exon 1 of 6 | 2 | ENSP00000409997.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD2 exomes AF: 0.00000455 AC: 1AN: 219570 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
219570
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451414Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 721274 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:
1451414
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
721274
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:
33270
American (AMR)
AF:
AC:
1
AN:
44064
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25906
East Asian (EAS)
AF:
AC:
0
AN:
39438
South Asian (SAS)
AF:
AC:
0
AN:
84646
European-Finnish (FIN)
AF:
AC:
0
AN:
50874
Middle Eastern (MID)
AF:
AC:
0
AN:
4400
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1108990
Other (OTH)
AF:
AC:
0
AN:
59826
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000081), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.300
Heterozygous variant carriers
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0
1
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type 7 Benign:1
Jun 16, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
RBP_binding_hub_radar
RBP_regulation_power_radar
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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