NM_006371.5:c.18_33delGGGGGCCGCGGCGCTG

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_006371.5(CRTAP):c.18_33delGGGGGCCGCGGCGCTG(p.Gly7fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,310,866 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 2.06

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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

CRTAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 16 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 54 pathogenic variants in the truncated region.

PP5

Variant 3-33114093-CGGGGGGCCGCGGCGCT-C is Pathogenic according to our data. Variant chr3-33114093-CGGGGGGCCGCGGCGCT-C is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 1070167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006371.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTAP	NM_006371.5	MANE Select	c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 7	NP_006362.1	O75718
CRTAP	NM_001393363.1		c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 6	NP_001380292.1
CRTAP	NM_001393364.1		c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 6	NP_001380293.1	C9JP16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTAP	ENST00000320954.11	TSL:1 MANE Select	c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 7	ENSP00000323696.5	O75718
CRTAP	ENST00000946650.1		c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 7	ENSP00000616709.1
CRTAP	ENST00000946648.1		c.18_33delGGGGGCCGCGGCGCTG	p.Gly7fs	frameshift	Exon 1 of 7	ENSP00000616707.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000109

AC:

AN:

73368

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000664

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000839

AC:

AN:

1310866

Hom.:

AF XY:

0.00000464

AC XY:

AN XY:

647122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26266

American (AMR)

AF:

0.000468

AC:

AN:

23514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22588

East Asian (EAS)

AF:

0.00

AC:

AN:

28830

South Asian (SAS)

AF:

0.00

AC:

AN:

70990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1046886

Other (OTH)

AF:

0.00

AC:

AN:

54252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.620

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Pathogenic/Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis imperfecta type 7 (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=27/173

disease causing (fs/PTC)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over