rs4678478

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006371.5(CRTAP):​c.*3891C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 152,336 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0072 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAPNM_006371.5 linkuse as main transcriptc.*3891C>A 3_prime_UTR_variant 7/7 ENST00000320954.11 NP_006362.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAPENST00000320954.11 linkuse as main transcriptc.*3891C>A 3_prime_UTR_variant 7/71 NM_006371.5 ENSP00000323696 P1
ENST00000607832.1 linkuse as main transcriptn.166+1217G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00281
AC:
427
AN:
152080
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00982
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00335
GnomAD4 exome
AF:
0.00725
AC:
1
AN:
138
Hom.:
0
Cov.:
0
AF XY:
0.00962
AC XY:
1
AN XY:
104
show subpopulations
Gnomad4 AFR exome
AF:
0.250
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00282
AC:
429
AN:
152198
Hom.:
2
Cov.:
33
AF XY:
0.00267
AC XY:
199
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.00984
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00332

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 7 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 28, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.0
DANN
Benign
0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4678478; hg19: chr3-33187831; API