Variant 3-33114093-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_006371.5(CRTAP):c.16C>A(p.Arg6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.0640

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-33114093-C-A is Benign according to our data. Variant chr3-33114093-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1702002.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-0.064 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CRTAP	NM_006371.5 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/6		NP_001380292.1
CRTAP	NM_001393364.1 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/6		NP_001380293.1
CRTAP	NM_001393365.1 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/7	1	NM_006371.5	ENSP00000323696	P1
CRTAP	ENST00000449224.1 linkuse as main transcript	c.16C>A	p.Arg6=	synonymous_variant	1/6	2		ENSP00000409997

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.63e-7

AC:

AN:

1310866

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

647122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Osteogenesis imperfecta

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 01, 2018

- -

Osteogenesis imperfecta type 7

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.1

DANN

Benign

0.57

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.4

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over