rs1369155614

Variant names:

• chr3-33114033-T-C
• rs1369155614
• NM_006371.5:c.-45T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-33114033-T-C
• chr3-33114033-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006371.5(CRTAP):​c.-45T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000325 in 1,230,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CRTAP NM_006371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.-45T>C		5_prime_UTR	Exon 1 of 7	NP_006362.1	O75718
	CRTAP	NM_001393363.1		c.-45T>C		5_prime_UTR	Exon 1 of 6	NP_001380292.1
	CRTAP	NM_001393364.1		c.-45T>C		5_prime_UTR	Exon 1 of 6	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.-45T>C		5_prime_UTR	Exon 1 of 7	ENSP00000323696.5	O75718
	CRTAP	ENST00000946647.1		c.-45T>C		5_prime_UTR	Exon 1 of 7	ENSP00000616706.1
	CRTAP	ENST00000858647.1		c.-45T>C		5_prime_UTR	Exon 1 of 6	ENSP00000528706.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000325 AC: 4 AN: 1230062 Hom.: 0 Cov.: 19 AF XY: 0.00000492 AC XY: 3 AN XY: 609706

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000415 AC: 1 AN: 24086

American (AMR) AF: 0.00 AC: 0 AN: 19690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21046

East Asian (EAS) AF: 0.00 AC: 0 AN: 27696

South Asian (SAS) AF: 0.00 AC: 0 AN: 66500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3756

European-Non Finnish (NFE) AF: 0.00000305 AC: 3 AN: 984168

Other (OTH) AF: 0.00 AC: 0 AN: 51208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.11
PromoterAI		-0.0047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1369155614; hg19: chr3-33155525;