NM_000093.5:c.110-14707C>T

Variant names:

• chr9-134676205-C-T
• rs7044529
• NM_000093.5:c.110-14707C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000093.5(COL5A1):​c.110-14707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,096 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3960 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 44 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 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.110-14707C>T		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.110-14707C>T		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.110-14707C>T		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000371820.4	TSL:2	c.110-14707C>T		intron	N/A	ENSP00000360885.4
	COL5A1	ENST00000464187.1	TSL:2	n.296-14707C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31839 AN: 151978 Hom.: 3954 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31879 AN: 152096 Hom.: 3960 Cov.: 32 AF XY: 0.213 AC XY: 15864 AN XY: 74354

African (AFR) AF: 0.333 AC: 13816 AN: 41450

American (AMR) AF: 0.214 AC: 3267 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.111 AC: 574 AN: 5170

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4824

European-Finnish (FIN) AF: 0.248 AC: 2625 AN: 10574

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9692 AN: 68006

Other (OTH) AF: 0.189 AC: 397 AN: 2106

Alfa AF: 0.157 Hom.: 9050

Bravo AF: 0.210

Asia WGS AF: 0.206 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-2.2
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: rs7044529; hg19: chr9-137568051;