rs11103544

Variant names:

• chr9-134843197-T-C
• rs11103544
• NM_000093.5:c.*894T>C

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.*894T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,912 control chromosomes in the GnomAD database, including 3,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3866 hom., cov: 31)
  • Exomes 𝑓: 0.056 (1 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.61
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-134843197-T-C is Benign according to our data. Variant chr9-134843197-T-C is described in ClinVar as Benign. ClinVar VariationId is 365765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.*894T>C		3_prime_UTR_variant	Exon 66 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.*894T>C		3_prime_UTR_variant	Exon 66 of 66		NP_001265003.1
LOC101448202	NR_103451.2	n.71-22988A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.*894T>C		3_prime_UTR_variant	Exon 66 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.*894T>C		3_prime_UTR_variant	Exon 66 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31380 AN: 151566 Hom.: 3857 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.0556 AC: 13 AN: 234 Hom.: 1 Cov.: 0 AF XY: 0.0714 AC XY: 10 AN XY: 140

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: 0.0556 AC: 13 AN: 234

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.207 AC: 31427 AN: 151678 Hom.: 3866 Cov.: 31 AF XY: 0.206 AC XY: 15237 AN XY: 74112

African (AFR) AF: 0.347 AC: 14287 AN: 41220

American (AMR) AF: 0.143 AC: 2175 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3460

East Asian (EAS) AF: 0.218 AC: 1123 AN: 5156

South Asian (SAS) AF: 0.275 AC: 1316 AN: 4780

European-Finnish (FIN) AF: 0.103 AC: 1086 AN: 10542

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10259 AN: 67958

Other (OTH) AF: 0.175 AC: 369 AN: 2108

Alfa AF: 0.168 Hom.: 4066

Bravo AF: 0.213

Asia WGS AF: 0.220 AC: 763 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.64
PhyloP100		1.6
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: rs11103544; hg19: chr9-137735043;