3-33120406-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006371.5(CRTAP):c.534C>T(p.Asp178Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,334 control chromosomes in the GnomAD database, including 20,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3785 hom., cov: 32)

Exomes 𝑓: 0.12 ( 17209 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.934

Publications

31 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

CRTAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 3-33120406-C-T is Benign according to our data. Variant chr3-33120406-C-T is described in ClinVar as [Benign]. Clinvar id is 195265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.934 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAP	NM_006371.5 link	c.534C>T	p.Asp178Asp	synonymous_variant	Exon 2 of 7	ENST00000320954.11	NP_006362.1	O75718
CRTAP	NM_001393363.1 link	c.534C>T	p.Asp178Asp	synonymous_variant	Exon 2 of 6		NP_001380292.1
CRTAP	NM_001393364.1 link	c.534C>T	p.Asp178Asp	synonymous_variant	Exon 2 of 6		NP_001380293.1
CRTAP	NM_001393365.1 link	c.472-4002C>T		intron_variant	Intron 1 of 5		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRTAP	ENST00000320954.11 link	c.534C>T	p.Asp178Asp	synonymous_variant	Exon 2 of 7	1	NM_006371.5	ENSP00000323696.5	O75718
CRTAP	ENST00000449224.1 link	c.534C>T	p.Asp178Asp	synonymous_variant	Exon 2 of 6	2		ENSP00000409997.1	C9JP16
CRTAP	ENST00000485310.1 link	n.128C>T		non_coding_transcript_exon_variant	Exon 2 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27912

AN:

151982

Hom.:

3770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.0874

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.172

AC:

42717

AN:

249034

AF XY:

0.164

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.0872

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.120

AC:

174656

AN:

1461234

Hom.:

17209

Cov.:

AF XY:

0.120

AC XY:

87515

AN XY:

726954

show subpopulations

African (AFR)

AF:

0.322

AC:

10776

AN:

33452

American (AMR)

AF:

0.156

AC:

6976

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3065

AN:

26134

East Asian (EAS)

AF:

0.606

AC:

24060

AN:

39686

South Asian (SAS)

AF:

0.180

AC:

15552

AN:

86236

European-Finnish (FIN)

AF:

0.185

AC:

9906

AN:

53420

Middle Eastern (MID)

AF:

0.124

AC:

712

AN:

5762

European-Non Finnish (NFE)

AF:

0.0856

AC:

95115

AN:

1111462

Other (OTH)

AF:

0.141

AC:

8494

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7168

14335

21503

28670

35838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.184

AC:

27973

AN:

152100

Hom.:

3785

Cov.:

AF XY:

0.191

AC XY:

14218

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.317

AC:

13149

AN:

41472

American (AMR)

AF:

0.131

AC:

1997

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3470

East Asian (EAS)

AF:

0.579

AC:

2998

AN:

5176

South Asian (SAS)

AF:

0.204

AC:

984

AN:

4826

European-Finnish (FIN)

AF:

0.195

AC:

2056

AN:

10560

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0874

AC:

5944

AN:

68010

Other (OTH)

AF:

0.161

AC:

340

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1042

2084

3126

4168

5210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.122

Hom.:

7585

Bravo

AF:

0.189

Asia WGS

AF:

0.350

AC:

1216

AN:

3478

EpiCase

AF:

0.0885

EpiControl

AF:

0.0843

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 17, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 14, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Osteogenesis imperfecta type 7

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.34

(source)

DANN

Benign

0.46

PhyloP100

-0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-33120406-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over