Variant 3-33146339-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAP	NM_006371.5 linkuse as main transcript	c.*3891C>T		3_prime_UTR_variant	7/7	ENST00000320954.11	NP_006362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11 linkuse as main transcript	c.*3891C>T		3_prime_UTR_variant	7/7	1	NM_006371.5	ENSP00000323696	P1
	ENST00000607832.1 linkuse as main transcript	n.166+1217G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.232

AC:

35225

AN:

152152

Hom.:

5051

Cov.:

AF XY:

0.244

AC XY:

18167

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.367

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.214

Hom.:

3774

Bravo

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Osteogenesis imperfecta type 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.6

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over