chr9-114156007-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032888.4(COL27A1):ā€‹c.57C>Gā€‹(p.Arg19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,145,638 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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.000020 ( 0 hom. )

Consequence

COL27A1
NM_032888.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0900
Variant links:
Genes affected
COL27A1 (HGNC:22986): (collagen type XXVII alpha 1 chain) This gene encodes a member of the fibrillar collagen family, and plays a role during the calcification of cartilage and the transition of cartilage to bone. The encoded protein product is a preproprotein. It includes an N-terminal signal peptide, which is followed by an N-terminal propetide, mature peptide and a C-terminal propeptide. The N-terminal propeptide contains thrombospondin N-terminal-like and laminin G-like domains. The mature peptide is a major triple-helical region. The C-terminal propeptide, also known as COLFI domain, plays crucial roles in tissue growth and repair. Mutations in this gene cause Steel syndrome. Alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Sep 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 9-114156007-C-G is Benign according to our data. Variant chr9-114156007-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1161100.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.09 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL27A1NM_032888.4 linkuse as main transcriptc.57C>G p.Arg19= synonymous_variant 1/61 ENST00000356083.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL27A1ENST00000356083.8 linkuse as main transcriptc.57C>G p.Arg19= synonymous_variant 1/611 NM_032888.4 P1Q8IZC6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000201
AC:
23
AN:
1145638
Hom.:
0
Cov.:
31
AF XY:
0.0000291
AC XY:
16
AN XY:
549246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000242
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 20, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
10
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs941086447; hg19: chr9-116918287; API