Genetic Variant CRTAP:c.*3891C>T (chr3-33146339-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006371.5(CRTAP):c.*3891C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,290 control chromosomes in the GnomAD database, including 5,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5051 hom., cov: 33)

Exomes 𝑓: 0.21 ( 3 hom. )

Consequence

CRTAP
NM_006371.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0330

Publications

5 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:

ENSG00000272149 (HGNC:):

ENSG00000272149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-33146339-C-T is Benign according to our data. Variant chr3-33146339-C-T is described in ClinVar as Benign. ClinVar VariationId is 344875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAP	NM_006371.5	MANE Select	c.*3891C>T		3_prime_UTR	Exon 7 of 7	NP_006362.1	O75718

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAP	ENST00000320954.11	TSL:1 MANE Select	c.*3891C>T		3_prime_UTR	Exon 7 of 7	ENSP00000323696.5	O75718
	ENSG00000272149	ENST00000607832.1	TSL:3	n.166+1217G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35201

AN:

152034

Hom.:

5056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.210

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.192

AC XY:

AN XY:

104

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.186

AC:

AN:

102

Other (OTH)

AF:

0.188

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.232

AC:

35225

AN:

152152

Hom.:

5051

Cov.:

AF XY:

0.244

AC XY:

18167

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.104

AC:

4340

AN:

41542

American (AMR)

AF:

0.367

AC:

5604

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

595

AN:

3470

East Asian (EAS)

AF:

0.538

AC:

2769

AN:

5146

South Asian (SAS)

AF:

0.329

AC:

1584

AN:

4816

European-Finnish (FIN)

AF:

0.380

AC:

4012

AN:

10566

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15604

AN:

68012

Other (OTH)

AF:

0.209

AC:

442

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1325

2651

3976

5302

6627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.215

Hom.:

4996

Bravo

AF:

0.224

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Osteogenesis imperfecta type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.6

(source)

DANN

Benign

0.80

PhyloP100

0.033

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over