chr3-33114416-G-C

Variant names:

• chr3-33114416-G-C
• rs960380634
• NM_006371.5:c.339G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006371.5(CRTAP):​c.339G>C​(p.Leu113Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,550,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: CRTAP NM_006371.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.96
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-33114416-G-C is Benign according to our data. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-33114416-G-C is described in CliVar as Likely_benign. Clinvar id is 534211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.96 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAP	NM_006371.5	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 6		NP_001380292.1
CRTAP	NM_001393364.1	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 6		NP_001380293.1
CRTAP	NM_001393365.1	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 7	1	NM_006371.5	ENSP00000323696.5
CRTAP	ENST00000449224.1	c.339G>C	p.Leu113Leu	synonymous_variant	Exon 1 of 6	2		ENSP00000409997.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000203 AC: 3 AN: 147662 AF XY: 0.00

Gnomad AFR exome AF: 0.000365

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000244

GnomAD4 exome AF: 0.00000858 AC: 12 AN: 1397910 Hom.: 0 Cov.: 32 AF XY: 0.00000579 AC XY: 4 AN XY: 691166

African (AFR) AF: 0.000362 AC: 11 AN: 30416

American (AMR) AF: 0.00 AC: 0 AN: 37388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24932

East Asian (EAS) AF: 0.00 AC: 0 AN: 35978

South Asian (SAS) AF: 0.00 AC: 0 AN: 79856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4320

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084248

Other (OTH) AF: 0.0000173 AC: 1 AN: 57944

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74360

African (AFR) AF: 0.000121 AC: 5 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Osteogenesis imperfecta type 7 Benign:1

Apr 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		3.0
PromoterAI		0.0084	Neutral

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: rs960380634; hg19: chr3-33155908;