rs1135128

Variant names:

• chr3-33132676-G-A
• rs1135128
• NM_006371.5:c.1044G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006371.5(CRTAP):​c.1044G>A​(p.Ser348Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,154 control chromosomes in the GnomAD database, including 136,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10571 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126413 hom.)
• Consequence: CRTAP NM_006371.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.88
• Publications: 23 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-33132676-G-A is Benign according to our data. Variant chr3-33132676-G-A is described in ClinVar as Benign. ClinVar VariationId is 259969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 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.1044G>A	p.Ser348Ser	synonymous	Exon 5 of 7	NP_006362.1	O75718
	CRTAP	NM_001393363.1		c.1044G>A	p.Ser348Ser	synonymous	Exon 5 of 6	NP_001380292.1
	CRTAP	NM_001393364.1		c.915G>A	p.Ser305Ser	synonymous	Exon 4 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.1044G>A	p.Ser348Ser	synonymous	Exon 5 of 7	ENSP00000323696.5	O75718
	CRTAP	ENST00000946650.1		c.1077G>A	p.Ser359Ser	synonymous	Exon 5 of 7	ENSP00000616709.1
	CRTAP	ENST00000946648.1		c.1044G>A	p.Ser348Ser	synonymous	Exon 5 of 7	ENSP00000616707.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54816 AN: 151946 Hom.: 10573 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.369 AC: 92871 AN: 251470 AF XY: 0.383

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.409 AC: 597731 AN: 1460090 Hom.: 126413 Cov.: 41 AF XY: 0.412 AC XY: 299267 AN XY: 726452

African (AFR) AF: 0.264 AC: 8814 AN: 33446

American (AMR) AF: 0.219 AC: 9802 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 13904 AN: 26118

East Asian (EAS) AF: 0.121 AC: 4785 AN: 39688

South Asian (SAS) AF: 0.413 AC: 35617 AN: 86206

European-Finnish (FIN) AF: 0.397 AC: 21199 AN: 53402

Middle Eastern (MID) AF: 0.509 AC: 2916 AN: 5728

European-Non Finnish (NFE) AF: 0.429 AC: 476362 AN: 1110474

Other (OTH) AF: 0.403 AC: 24332 AN: 60308

GnomAD4 genome AF: 0.360 AC: 54818 AN: 152064 Hom.: 10571 Cov.: 32 AF XY: 0.358 AC XY: 26596 AN XY: 74312

African (AFR) AF: 0.261 AC: 10814 AN: 41476

American (AMR) AF: 0.304 AC: 4647 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3468

East Asian (EAS) AF: 0.137 AC: 712 AN: 5182

South Asian (SAS) AF: 0.380 AC: 1834 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4125 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29531 AN: 67948

Other (OTH) AF: 0.406 AC: 859 AN: 2116

Alfa AF: 0.409 Hom.: 11937

Bravo AF: 0.347

Asia WGS AF: 0.242 AC: 847 AN: 3478

EpiCase AF: 0.439

EpiControl AF: 0.453

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Osteogenesis imperfecta type 7 (5)
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.076
DANN	Benign	0.40
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1135128; hg19: chr3-33174168; COSMIC: COSV58013914; COSMIC: COSV58013914;