chr9-134843171-T-TAGGG

Variant names:

• chr9-134843171-T-TAGGG
• rs10628678
• NM_000093.5:c.*870_*873dupGGGA

Variant summary

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

The NM_000093.5(COL5A1):​c.*870_*873dupGGGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33260 hom., cov: 0)
  • Exomes 𝑓: 0.77 (60 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.491
• Publications: 21 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

LOC101448202 (HGNC:):

ACMG classification

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

• BP6: Variant 9-134843171-T-TAGGG is Benign according to our data. Variant chr9-134843171-T-TAGGG is described in ClinVar as Benign. ClinVar VariationId is 365764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.*870_*873dupGGGA		3_prime_UTR_variant	Exon 66 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.*870_*873dupGGGA		3_prime_UTR_variant	Exon 66 of 66		NP_001265003.1
LOC101448202	NR_103451.2	n.71-22966_71-22963dupCCCT		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.*870_*873dupGGGA		3_prime_UTR_variant	Exon 66 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.*870_*873dupGGGA		3_prime_UTR_variant	Exon 66 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.663 AC: 99225 AN: 149570 Hom.: 33246 Cov.: 0

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.765 AC: 150 AN: 196 Hom.: 60 Cov.: 0 AF XY: 0.767 AC XY: 92 AN XY: 120

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: 0.765 AC: 150 AN: 196

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.663 AC: 99277 AN: 149674 Hom.: 33260 Cov.: 0 AF XY: 0.660 AC XY: 48056 AN XY: 72828

African (AFR) AF: 0.630 AC: 25596 AN: 40618

American (AMR) AF: 0.601 AC: 9082 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2432 AN: 3452

East Asian (EAS) AF: 0.441 AC: 2242 AN: 5086

South Asian (SAS) AF: 0.643 AC: 3013 AN: 4688

European-Finnish (FIN) AF: 0.739 AC: 7301 AN: 9876

Middle Eastern (MID) AF: 0.741 AC: 215 AN: 290

European-Non Finnish (NFE) AF: 0.703 AC: 47514 AN: 67570

Other (OTH) AF: 0.678 AC: 1407 AN: 2076

Alfa AF: 0.637 Hom.: 3161

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10628678; hg19: chr9-137735017; COSMIC: COSV65664575;