rs12005720

chr9-134786174-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000093.5(COL5A1):c.2646+126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 927,386 control chromosomes in the GnomAD database, including 7,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1753 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5989 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.99).
• BP6: Variant 9-134786174-T-C is Benign according to our data. Variant chr9-134786174-T-C is described in ClinVar as [Benign]. Clinvar id is 1257326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.2646+126T>C		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.2646+126T>C		intron_variant
COL5A1	XM_017014266.3	c.2646+126T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.2646+126T>C		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.2646+126T>C		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21936 AN: 151868 Hom.: 1750 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.118 AC: 91139 AN: 775400 Hom.: 5989 AF XY: 0.116 AC XY: 46843 AN XY: 403004

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.0788

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0789

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.144 AC: 21962 AN: 151986 Hom.: 1753 Cov.: 32 AF XY: 0.142 AC XY: 10545 AN XY: 74300

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0722

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.146

Alfa AF: 0.126 Hom.: 497

Bravo AF: 0.142

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.47
Dann	Benign	0.19

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: rs12005720; hg19: chr9-137678020; COSMIC: COSV65667109;