GeneBe

NM_006371.5:c.339G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006371.5(CRTAP):​c.339G>T​(p.Leu113Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,910 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. L113L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96

Publications

0 publications found
Variant links:
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 7
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • osteogenesis imperfecta type 2
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • osteogenesis imperfecta type 3
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • osteogenesis imperfecta type 4
    Inheritance: 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=-0.55).
BP7
Synonymous conserved (PhyloP=2.96 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRTAPNM_006371.5 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 7 ENST00000320954.11 NP_006362.1 O75718
CRTAPNM_001393363.1 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 6 NP_001380292.1
CRTAPNM_001393364.1 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 6 NP_001380293.1
CRTAPNM_001393365.1 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 6 NP_001380294.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRTAPENST00000320954.11 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 7 1 NM_006371.5 ENSP00000323696.5 O75718
CRTAPENST00000449224.1 linkc.339G>T p.Leu113Leu synonymous_variant Exon 1 of 6 2 ENSP00000409997.1 C9JP16

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1397910
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
691166
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
30416
American (AMR)
AF:
0.00
AC:
0
AN:
37388
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24932
East Asian (EAS)
AF:
0.0000278
AC:
1
AN:
35978
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79856
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42828
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4320
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1084248
Other (OTH)
AF:
0.00
AC:
0
AN:
57944
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
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
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Benign
0.82
PhyloP100
3.0
PromoterAI
-0.039
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs960380634; hg19: chr3-33155908; API