9-134761890-C-A

Variant names:

• chr9-134761890-C-A
• rs10858278
• NM_000093.5:c.1936-35C>A

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.1936-35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,609,784 control chromosomes in the GnomAD database, including 8,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2264 hom., cov: 33)
  • Exomes 𝑓: 0.063 (6356 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.202
• Publications: 5 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=-0.85).
• BP6: Variant 9-134761890-C-A is Benign according to our data. Variant chr9-134761890-C-A is described in ClinVar as Benign. ClinVar VariationId is 255059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.1936-35C>A		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.1936-35C>A		intron	N/A	NP_001265003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.1936-35C>A		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000371820.4	TSL:2	c.1936-35C>A		intron	N/A	ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19955 AN: 152132 Hom.: 2257 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.116 AC: 28964 AN: 250734 AF XY: 0.104

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.0878

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.0338

Gnomad NFE exome AF: 0.0405

Gnomad OTH exome AF: 0.0876

GnomAD4 exome AF: 0.0627 AC: 91377 AN: 1457534 Hom.: 6356 Cov.: 30 AF XY: 0.0624 AC XY: 45262 AN XY: 725312

African (AFR) AF: 0.290 AC: 9667 AN: 33384

American (AMR) AF: 0.242 AC: 10819 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 2230 AN: 26098

East Asian (EAS) AF: 0.270 AC: 10694 AN: 39670

South Asian (SAS) AF: 0.118 AC: 10148 AN: 86196

European-Finnish (FIN) AF: 0.0344 AC: 1814 AN: 52722

Middle Eastern (MID) AF: 0.0823 AC: 474 AN: 5756

European-Non Finnish (NFE) AF: 0.0367 AC: 40741 AN: 1108762

Other (OTH) AF: 0.0795 AC: 4790 AN: 60244

GnomAD4 genome AF: 0.131 AC: 20008 AN: 152250 Hom.: 2264 Cov.: 33 AF XY: 0.132 AC XY: 9804 AN XY: 74444

African (AFR) AF: 0.286 AC: 11871 AN: 41518

American (AMR) AF: 0.168 AC: 2570 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.272 AC: 1408 AN: 5182

South Asian (SAS) AF: 0.120 AC: 581 AN: 4828

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10616

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2677 AN: 68022

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.106 Hom.: 397

Bravo AF: 0.151

Asia WGS AF: 0.212 AC: 734 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Fibromuscular dysplasia, multifocal Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.68
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs10858278; hg19: chr9-137653736; COSMIC: COSV65666812;