9-134843386-GCTATCTAT-GCTAT

Variant names:

• chr9-134843386-GCTAT-G
• rs16399
• NM_000093.5:c.*1090_*1093delATCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000093.5(COL5A1):​c.*1090_*1093delATCT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.663 in 151,922 control chromosomes in the GnomAD database, including 33,670 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33537 hom., cov: 0)
  • Exomes 𝑓: 0.76 (133 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.13
• Publications: 9 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: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
• 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

LOC101448202 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-134843386-GCTAT-G is Benign according to our data. Variant chr9-134843386-GCTAT-G is described in ClinVar as Benign. ClinVar VariationId is 365768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 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.*1090_*1093delATCT		3_prime_UTR	Exon 66 of 66	NP_000084.3
	COL5A1	NM_001278074.1		c.*1090_*1093delATCT		3_prime_UTR	Exon 66 of 66	NP_001265003.1	P20908-2
	LOC101448202	NR_103451.2		n.71-23181_71-23178delATAG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.*1090_*1093delATCT		3_prime_UTR	Exon 66 of 66	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.*1090_*1093delATCT		3_prime_UTR	Exon 66 of 66	ENSP00000360885.4	P20908-2
	COL5A1	ENST00000950240.1		c.*1090_*1093delATCT		3_prime_UTR	Exon 66 of 66	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100269 AN: 151340 Hom.: 33521 Cov.: 0

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.758 AC: 350 AN: 462 Hom.: 133 AF XY: 0.777 AC XY: 213 AN XY: 274

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.764 AC: 336 AN: 440

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.900 AC: 9 AN: 10

Other (OTH) AF: 0.400 AC: 4 AN: 10

GnomAD4 genome AF: 0.662 AC: 100330 AN: 151460 Hom.: 33537 Cov.: 0 AF XY: 0.659 AC XY: 48801 AN XY: 74002

African (AFR) AF: 0.630 AC: 25987 AN: 41232

American (AMR) AF: 0.599 AC: 9137 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2446 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2249 AN: 5132

South Asian (SAS) AF: 0.644 AC: 3093 AN: 4804

European-Finnish (FIN) AF: 0.740 AC: 7754 AN: 10474

Middle Eastern (MID) AF: 0.738 AC: 214 AN: 290

European-Non Finnish (NFE) AF: 0.701 AC: 47544 AN: 67810

Other (OTH) AF: 0.676 AC: 1423 AN: 2106

Alfa AF: 0.580 Hom.: 1600

Bravo AF: 0.647

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome type 7A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1
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: rs16399; hg19: chr9-137735232; COSMIC: COSV65664577;