9-134642008-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000093.5(COL5A1):c.-180C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 523,310 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (17 hom., cov: 32)
  • Exomes 𝑓: 0.012 (43 hom.)
• Consequence: COL5A1 NM_000093.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.973

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-134642008-C-A is Benign according to our data. Variant chr9-134642008-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0127 (1925/151868) while in subpopulation AMR AF= 0.0142 (217/15280). AF 95% confidence interval is 0.013. There are 17 homozygotes in gnomad4. There are 940 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1924 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.-180C>A		5_prime_UTR_variant	1/66	ENST00000371817.8
COL5A1	NM_001278074.1	c.-180C>A		5_prime_UTR_variant	1/66
COL5A1	XM_017014266.3	c.-180C>A		5_prime_UTR_variant	1/65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.-180C>A		5_prime_UTR_variant	1/66	1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.-180C>A		5_prime_UTR_variant	1/66	2		A2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1924 AN: 151760 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0168

GnomAD4 exome AF: 0.0120 AC: 4459 AN: 371442 Hom.: 43 Cov.: 5 AF XY: 0.0120 AC XY: 2208 AN XY: 184706

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000894

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome AF: 0.0127 AC: 1925 AN: 151868 Hom.: 17 Cov.: 32 AF XY: 0.0127 AC XY: 940 AN XY: 74226

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0145 Hom.: 3

Bravo AF: 0.0117

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	18
Dann	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs188194985; hg19: chr9-137533854;