9-114210993-C-T

Variant names:

• chr9-114210993-C-T
• rs34350265
• NM_032888.4:c.2334C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032888.4(COL27A1):​c.2334C>T​(p.Gly778Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,613,340 control chromosomes in the GnomAD database, including 5,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (675 hom., cov: 33)
  • Exomes 𝑓: 0.075 (4471 hom.)
• Consequence: COL27A1 NM_032888.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.263
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 9-114210993-C-T is Benign according to our data. Variant chr9-114210993-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.263 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032888.4. 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
	COL27A1	NM_032888.4	MANE Select	c.2334C>T	p.Gly778Gly	synonymous	Exon 12 of 61	NP_116277.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL27A1	ENST00000356083.8	TSL:1 MANE Select	c.2334C>T	p.Gly778Gly	synonymous	Exon 12 of 61	ENSP00000348385.3	Q8IZC6-1
	COL27A1	ENST00000451716.5	TSL:1	c.2022C>T	p.Gly674Gly	synonymous	Exon 7 of 8	ENSP00000391328.1	Q5T1U7
	COL27A1	ENST00000494090.6	TSL:1	n.1227C>T		non_coding_transcript_exon	Exon 9 of 58	ENSP00000432928.1	H0YD40

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13364 AN: 152170 Hom.: 674 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0967

GnomAD2 exomes AF: 0.0731 AC: 18385 AN: 251404 AF XY: 0.0733

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0464

Gnomad FIN exome AF: 0.0367

Gnomad NFE exome AF: 0.0792

Gnomad OTH exome AF: 0.0854

GnomAD4 exome AF: 0.0747 AC: 109077 AN: 1461052 Hom.: 4471 Cov.: 32 AF XY: 0.0748 AC XY: 54382 AN XY: 726858

African (AFR) AF: 0.129 AC: 4315 AN: 33450

American (AMR) AF: 0.0535 AC: 2392 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3994 AN: 26122

East Asian (EAS) AF: 0.0522 AC: 2072 AN: 39698

South Asian (SAS) AF: 0.0605 AC: 5216 AN: 86242

European-Finnish (FIN) AF: 0.0355 AC: 1895 AN: 53408

Middle Eastern (MID) AF: 0.115 AC: 665 AN: 5768

European-Non Finnish (NFE) AF: 0.0752 AC: 83605 AN: 1111280

Other (OTH) AF: 0.0816 AC: 4923 AN: 60364

GnomAD4 genome AF: 0.0878 AC: 13372 AN: 152288 Hom.: 675 Cov.: 33 AF XY: 0.0850 AC XY: 6331 AN XY: 74464

African (AFR) AF: 0.126 AC: 5224 AN: 41568

American (AMR) AF: 0.0708 AC: 1084 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.0525 AC: 271 AN: 5158

South Asian (SAS) AF: 0.0568 AC: 274 AN: 4824

European-Finnish (FIN) AF: 0.0335 AC: 356 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5364 AN: 68030

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

Alfa AF: 0.0830 Hom.: 1238

Bravo AF: 0.0919

Asia WGS AF: 0.0710 AC: 247 AN: 3478

EpiCase AF: 0.0823

EpiControl AF: 0.0870

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.8
DANN	Benign	0.88
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs34350265; hg19: chr9-116973273; COSMIC: COSV61921826; COSMIC: COSV61921826;