3-33146339-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CRTAP	NM_006371.5	c.*3891C>T		3_prime_UTR_variant	7/7	ENST00000320954.11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35201 AN: 152034 Hom.: 5056 Cov.: 33

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: 29 AN: 138 Hom.: 3 Cov.: 0 AF XY: 0.192 AC XY: 20 AN XY: 104

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.: 33 AF XY: 0.244 AC XY: 18167 AN XY: 74374

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Other links and lift over

dbSNP: rs4678478; hg19: chr3-33187831;