Genetic Variant NM_006371.5:c.18G>A (chr3-33114095-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006371.5(CRTAP):c.18G>A(p.Arg6Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,312,510 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. Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.547

Publications

0 publications found

Variant links:

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

CRTAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=0.547 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTAP	NM_006371.5	MANE Select	c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 7	NP_006362.1	O75718
CRTAP	NM_001393363.1		c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 6	NP_001380292.1
CRTAP	NM_001393364.1		c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 6	NP_001380293.1	C9JP16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTAP	ENST00000320954.11	TSL:1 MANE Select	c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 7	ENSP00000323696.5	O75718
CRTAP	ENST00000946650.1		c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 7	ENSP00000616709.1
CRTAP	ENST00000946648.1		c.18G>A	p.Arg6Arg	synonymous	Exon 1 of 7	ENSP00000616707.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000267

AC:

AN:

74990

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000674

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1312510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26362

American (AMR)

AF:

0.00

AC:

AN:

23586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22694

East Asian (EAS)

AF:

0.00

AC:

AN:

28892

South Asian (SAS)

AF:

0.00

AC:

AN:

71258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4598

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1047770

Other (OTH)

AF:

0.00

AC:

AN:

54310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.7

(source)

DANN

Benign

0.86

PhyloP100

0.55

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over