9-134795060-C-T

Variant names:

• chr9-134795060-C-T
• rs4072883
• NM_000093.5:c.2701-22C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.2701-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,609,636 control chromosomes in the GnomAD database, including 281,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33155 hom., cov: 32)
  • Exomes 𝑓: 0.58 (248811 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.278
• Publications: 14 publications found

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-134795060-C-T is Benign according to our data. Variant chr9-134795060-C-T is described in ClinVar as Benign. ClinVar VariationId is 255069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. 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
	COL5A1	NM_000093.5	MANE Select	c.2701-22C>T		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.2701-22C>T		intron	N/A	NP_001265003.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.2701-22C>T		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000371820.4	TSL:2	c.2701-22C>T		intron	N/A	ENSP00000360885.4
	COL5A1	ENST00000950240.1		c.2692-22C>T		intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98523 AN: 151908 Hom.: 33113 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.631

GnomAD2 exomes AF: 0.604 AC: 151063 AN: 250244 AF XY: 0.597

Gnomad AFR exome AF: 0.844

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.834

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.580 AC: 845558 AN: 1457608 Hom.: 248811 Cov.: 39 AF XY: 0.580 AC XY: 420389 AN XY: 725372

African (AFR) AF: 0.848 AC: 28370 AN: 33442

American (AMR) AF: 0.534 AC: 23868 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 15912 AN: 26112

East Asian (EAS) AF: 0.800 AC: 31763 AN: 39684

South Asian (SAS) AF: 0.568 AC: 48961 AN: 86174

European-Finnish (FIN) AF: 0.548 AC: 29173 AN: 53228

Middle Eastern (MID) AF: 0.604 AC: 3477 AN: 5760

European-Non Finnish (NFE) AF: 0.566 AC: 627660 AN: 1108256

Other (OTH) AF: 0.604 AC: 36374 AN: 60248

GnomAD4 genome AF: 0.649 AC: 98624 AN: 152028 Hom.: 33155 Cov.: 32 AF XY: 0.645 AC XY: 47896 AN XY: 74292

African (AFR) AF: 0.832 AC: 34494 AN: 41468

American (AMR) AF: 0.542 AC: 8280 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3470

East Asian (EAS) AF: 0.822 AC: 4240 AN: 5158

South Asian (SAS) AF: 0.574 AC: 2757 AN: 4806

European-Finnish (FIN) AF: 0.553 AC: 5838 AN: 10554

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39049 AN: 67980

Other (OTH) AF: 0.630 AC: 1331 AN: 2112

Alfa AF: 0.631 Hom.: 13308

Bravo AF: 0.659

Asia WGS AF: 0.720 AC: 2503 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ehlers-Danlos syndrome, classic type, 1 (1)
-	-	1	Fibromuscular dysplasia, multifocal (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.28
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: rs4072883; hg19: chr9-137686906; COSMIC: COSV65667137;