rs11103502

Positions:

• chr9-134754371-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.1827+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,609,864 control chromosomes in the GnomAD database, including 27,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2096 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25444 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.35

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 9-134754371-G-A is Benign according to our data. Variant chr9-134754371-G-A is described in ClinVar as [Benign]. Clinvar id is 255057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.1827+45G>A		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.1827+45G>A		intron_variant
COL5A1	XM_017014266.3	c.1827+45G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.1827+45G>A		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.1827+45G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23455 AN: 152080 Hom.: 2094 Cov.: 33

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.169 AC: 42062 AN: 249332 Hom.: 4135 AF XY: 0.170 AC XY: 23016 AN XY: 135234

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.0919

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.182 AC: 265200 AN: 1457666 Hom.: 25444 Cov.: 32 AF XY: 0.181 AC XY: 131104 AN XY: 725430

Gnomad4 AFR exome AF: 0.0842

Gnomad4 AMR exome AF: 0.0963

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.154 AC: 23446 AN: 152198 Hom.: 2096 Cov.: 33 AF XY: 0.155 AC XY: 11551 AN XY: 74404

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.151

Alfa AF: 0.160 Hom.: 382

Bravo AF: 0.150

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0040
DANN	Benign	0.62

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: rs11103502; hg19: chr9-137646217; COSMIC: COSV65666825;