rs1135128

Positions:

chr3-33132676-G-A

Variant summary

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

The NM_006371.5(CRTAP):c.1044G>A(p.Ser348=) 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

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:

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=-0.73).

BP6

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

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/exons	MANE	Protein
CRTAP	NM_006371.5 linkuse as main transcript	c.1044G>A	p.Ser348=	synonymous_variant	5/7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1 linkuse as main transcript	c.1044G>A	p.Ser348=	synonymous_variant	5/6		NP_001380292.1
CRTAP	NM_001393364.1 linkuse as main transcript	c.915G>A	p.Ser305=	synonymous_variant	4/6		NP_001380293.1
CRTAP	NM_001393365.1 linkuse as main transcript	c.894G>A	p.Ser298=	synonymous_variant	4/6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11 linkuse as main transcript	c.1044G>A	p.Ser348=	synonymous_variant	5/7	1	NM_006371.5	ENSP00000323696	P1
CRTAP	ENST00000449224.1 linkuse as main transcript	c.915G>A	p.Ser305=	synonymous_variant	4/6	2		ENSP00000409997

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

GnomAD3 exomes

AF:

0.369

AC:

92871

AN:

251470

Hom.:

18821

AF XY:

0.383

AC XY:

52022

AN XY:

135908

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 SAS exome

AF:

0.412

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

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.360

AC:

54818

AN:

152064

Hom.:

10571

Cov.:

AF XY:

0.358

AC XY:

26596

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.525

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.435

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.410

Hom.:

9123

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.076

DANN

Benign

0.40

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