rs13637

Positions:

• chr3-33130033-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006371.5(CRTAP):​c.888C>T​(p.Thr296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000854 in 1,613,768 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (9 hom., cov: 30)
  • Exomes 𝑓: 0.00046 (5 hom.)
• Consequence: CRTAP NM_006371.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.928

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 3-33130033-C-T is Benign according to our data. Variant chr3-33130033-C-T is described in ClinVar as [Benign]. Clinvar id is 465816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.928 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (710/152260) while in subpopulation AFR AF= 0.0161 (671/41548). AF 95% confidence interval is 0.0151. There are 9 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAP	NM_006371.5	c.888C>T	p.Thr296=	synonymous_variant	4/7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1	c.888C>T	p.Thr296=	synonymous_variant	4/6		NP_001380292.1
CRTAP	NM_001393365.1	c.738C>T	p.Thr246=	synonymous_variant	3/6		NP_001380294.1
CRTAP	NM_001393364.1	c.794-2522C>T		intron_variant			NP_001380293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11	c.888C>T	p.Thr296=	synonymous_variant	4/7	1	NM_006371.5	ENSP00000323696	P1
CRTAP	ENST00000449224.1	c.794-2522C>T		intron_variant		2		ENSP00000409997
CRTAP	ENST00000485310.1	n.482C>T		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152142 Hom.: 9 Cov.: 30

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00115 AC: 289 AN: 251454 Hom.: 4 AF XY: 0.000861 AC XY: 117 AN XY: 135894

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000457 AC: 668 AN: 1461508 Hom.: 5 Cov.: 31 AF XY: 0.000433 AC XY: 315 AN XY: 727080

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.00466 AC: 710 AN: 152260 Hom.: 9 Cov.: 30 AF XY: 0.00457 AC XY: 340 AN XY: 74462

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00534

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Osteogenesis imperfecta type 7 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	10
DANN	Benign	0.71
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

Other links and lift over

dbSNP: rs13637; hg19: chr3-33171525;