rs368011067

Variant names:

• chr9-134818715-C-A
• rs368011067
• NM_000093.5:c.4290C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134818715-C-A
• chr9-134818715-C-G
• chr9-134818715-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000093.5(COL5A1):​c.4290C>A​(p.Ala1430Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,006 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. Synonymous variant affecting the same amino acid position (i.e. A1430A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL5A1 NM_000093.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 0 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, PanelApp Australia, Genomics England PanelApp, Ambry Genetics
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BS2: High AC in GnomAd4 at 22 AD gene.

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.4290C>A	p.Ala1430Ala	synonymous	Exon 55 of 66	NP_000084.3
	COL5A1	NM_001278074.1		c.4290C>A	p.Ala1430Ala	synonymous	Exon 55 of 66	NP_001265003.1	P20908-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.4290C>A	p.Ala1430Ala	synonymous	Exon 55 of 66	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.4290C>A	p.Ala1430Ala	synonymous	Exon 55 of 66	ENSP00000360885.4	P20908-2
	COL5A1	ENST00000950240.1		c.4281C>A	p.Ala1427Ala	synonymous	Exon 55 of 66	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151970 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240926 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000928

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459036 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725740

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111250

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151970 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.000249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.0
DANN	Benign	0.63
PhyloP100		0.26

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: rs368011067; hg19: chr9-137710561;