rs7623768

chr3-33140560-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006371.5(CRTAP):c.1153-1835A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,174 control chromosomes in the GnomAD database, including 2,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2030 hom., cov: 33)
• Consequence: CRTAP NM_006371.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTAP	NM_006371.5	c.1153-1835A>C		intron_variant		ENST00000320954.11
CRTAP	NM_001393363.1	c.1069-1835A>C		intron_variant
CRTAP	NM_001393364.1	c.1024-1835A>C		intron_variant
CRTAP	NM_001393365.1	c.1003-1835A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTAP	ENST00000320954.11	c.1153-1835A>C		intron_variant		1	NM_006371.5	P1
CRTAP	ENST00000449224.1	c.1024-1835A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24007 AN: 152056 Hom.: 2023 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24035 AN: 152174 Hom.: 2030 Cov.: 33 AF XY: 0.160 AC XY: 11869 AN XY: 74402

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.161

Alfa AF: 0.165 Hom.: 4432

Bravo AF: 0.160

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.42
Dann	Benign	0.40

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: rs7623768; hg19: chr3-33182052;