rs35357409

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006371.5(CRTAP):c.558A>G(p.Ala186Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,613,268 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 171 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 180 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.14

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:

CRTAP (HGNC:):

CRTAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-33120430-A-G is Benign according to our data. Variant chr3-33120430-A-G is described in ClinVar as [Benign]. Clinvar id is 195266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-33120430-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0904 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.558A>G	p.Ala186Ala	synonymous_variant	2/7	ENST00000320954.11	NP_006362.1	O75718
CRTAP	NM_001393363.1 linkuse as main transcript	c.558A>G	p.Ala186Ala	synonymous_variant	2/6		NP_001380292.1
CRTAP	NM_001393364.1 linkuse as main transcript	c.558A>G	p.Ala186Ala	synonymous_variant	2/6		NP_001380293.1
CRTAP	NM_001393365.1 linkuse as main transcript	c.472-3978A>G		intron_variant			NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRTAP	ENST00000320954.11 linkuse as main transcript	c.558A>G	p.Ala186Ala	synonymous_variant	2/7	1	NM_006371.5	ENSP00000323696.5	O75718
CRTAP	ENST00000449224.1 linkuse as main transcript	c.558A>G	p.Ala186Ala	synonymous_variant	2/6	2		ENSP00000409997.1	C9JP16
CRTAP	ENST00000485310.1 linkuse as main transcript	n.152A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4186

AN:

152198

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00822

AC:

2046

AN:

249022

Hom.:

AF XY:

0.00605

AC XY:

815

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.0921

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0162

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00621

GnomAD4 exome

AF:

0.00349

AC:

5102

AN:

1460952

Hom.:

180

Cov.:

AF XY:

0.00311

AC XY:

2257

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.0963

Gnomad4 AMR exome

AF:

0.00521

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0185

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000301

Gnomad4 OTH exome

AF:

0.00784

GnomAD4 genome

AF:

0.0276

AC:

4198

AN:

152316

Hom.:

171

Cov.:

AF XY:

0.0264

AC XY:

1970

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0928

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0173

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00852

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 7

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 27, 2016	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.027

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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