rs1848091276

Variant names:

• chr9-114155961-G-A
• rs1848091276
• NM_032888.4:c.11G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-114155961-G-A
• chr9-114155961-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032888.4(COL27A1):​c.11G>A​(p.Gly4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000884 in 1,131,336 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: COL27A1 NM_032888.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

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]

COL27A1 Gene-Disease associations (from GenCC):

• Steel syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19097331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.11G>A	p.Gly4Glu	missense_variant	Exon 1 of 61	ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.11G>A	p.Gly4Glu	missense_variant	Exon 1 of 61	1	NM_032888.4	ENSP00000348385.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.84e-7 AC: 1 AN: 1131336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 540848

African (AFR) AF: 0.00 AC: 0 AN: 24422

American (AMR) AF: 0.00 AC: 0 AN: 15460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14832

East Asian (EAS) AF: 0.00 AC: 0 AN: 30038

South Asian (SAS) AF: 0.0000390 AC: 1 AN: 25616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 943950

Other (OTH) AF: 0.00 AC: 0 AN: 45290

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.28
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.017	D
Polyphen		0.018	B
Vest4		0.22
MutPred		0.24		Loss of MoRF binding (P = 0.0174);
MVP		0.082
MPC		0.15
ClinPred		0.49	T
GERP RS		2.4
PromoterAI		0.059	Neutral
Varity_R		0.14
gMVP		0.32
Mutation Taster		=90/10	polymorphism

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: rs1848091276; hg19: chr9-116918241;