chr3-33140560-A-C

Variant names:

• chr3-33140560-A-C
• rs7623768
• NM_006371.5:c.1153-1835A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 7

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006371.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAP	NM_006371.5	MANE Select	c.1153-1835A>C		intron	N/A	NP_006362.1	O75718
	CRTAP	NM_001393363.1		c.1069-1835A>C		intron	N/A	NP_001380292.1
	CRTAP	NM_001393364.1		c.1024-1835A>C		intron	N/A	NP_001380293.1	C9JP16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAP	ENST00000320954.11	TSL:1 MANE Select	c.1153-1835A>C		intron	N/A	ENSP00000323696.5	O75718
	CRTAP	ENST00000946650.1		c.1186-1835A>C		intron	N/A	ENSP00000616709.1
	CRTAP	ENST00000946648.1		c.1157-1842A>C		intron	N/A	ENSP00000616707.1

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

African (AFR) AF: 0.126 AC: 5241 AN: 41510

American (AMR) AF: 0.168 AC: 2562 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1431 AN: 5184

South Asian (SAS) AF: 0.195 AC: 941 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10894 AN: 67998

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.164 Hom.: 9428

Bravo AF: 0.160

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7623768; hg19: chr3-33182052;