rs1135128

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006371.5(CRTAP):c.1044G>A(p.Ser348Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,154 control chromosomes in the GnomAD database, including 136,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10571 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126413 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.88

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-33132676-G-A is Benign according to our data. Variant chr3-33132676-G-A is described in ClinVar as Benign. ClinVar VariationId is 259969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CRTAP	NM_006371.5 link	c.1044G>A	p.Ser348Ser	synonymous_variant	Exon 5 of 7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1 link	c.1044G>A	p.Ser348Ser	synonymous_variant	Exon 5 of 6		NP_001380292.1
CRTAP	NM_001393364.1 link	c.915G>A	p.Ser305Ser	synonymous_variant	Exon 4 of 6		NP_001380293.1
CRTAP	NM_001393365.1 link	c.894G>A	p.Ser298Ser	synonymous_variant	Exon 4 of 6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CRTAP	ENST00000320954.11 link	c.1044G>A	p.Ser348Ser	synonymous_variant	Exon 5 of 7	1	NM_006371.5	ENSP00000323696.5
CRTAP	ENST00000449224.1 link	c.915G>A	p.Ser305Ser	synonymous_variant	Exon 4 of 6	2		ENSP00000409997.1
CRTAP	ENST00000485310.1 link	n.*76G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54816

AN:

151946

Hom.:

10573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.409

GnomAD2 exomes

AF:

0.369

AC:

92871

AN:

251470

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.409

AC:

597731

AN:

1460090

Hom.:

126413

Cov.:

AF XY:

0.412

AC XY:

299267

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.264

AC:

8814

AN:

33446

American (AMR)

AF:

0.219

AC:

9802

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

13904

AN:

26118

East Asian (EAS)

AF:

0.121

AC:

4785

AN:

39688

South Asian (SAS)

AF:

0.413

AC:

35617

AN:

86206

European-Finnish (FIN)

AF:

0.397

AC:

21199

AN:

53402

Middle Eastern (MID)

AF:

0.509

AC:

2916

AN:

5728

European-Non Finnish (NFE)

AF:

0.429

AC:

476362

AN:

1110474

Other (OTH)

AF:

0.403

AC:

24332

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

18366

36732

55098

73464

91830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14234

28468

42702

56936

71170

<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

AF:

0.360

AC:

54818

AN:

152064

Hom.:

10571

Cov.:

AF XY:

0.358

AC XY:

26596

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.261

AC:

10814

AN:

41476

American (AMR)

AF:

0.304

AC:

4647

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1822

AN:

3468

East Asian (EAS)

AF:

0.137

AC:

712

AN:

5182

South Asian (SAS)

AF:

0.380

AC:

1834

AN:

4826

European-Finnish (FIN)

AF:

0.390

AC:

4125

AN:

10564

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29531

AN:

67948

Other (OTH)

AF:

0.406

AC:

859

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1762

3523

5285

7046

8808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.409

Hom.:

11937

Bravo

AF:

0.347

Asia WGS

AF:

0.242

AC:

847

AN:

3478

EpiCase

AF:

0.439

EpiControl

AF:

0.453

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 7

Benign:5

Jan 12, 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.

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:3

Mar 03, 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.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.73

CADD

Benign

0.076

(source)

DANN

Benign

0.40

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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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