rs3811147

Positions:

• chr9-134820071-G-A
• chr9-134820071-G-C

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.4447-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,463,016 control chromosomes in the GnomAD database, including 1,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (399 hom., cov: 33)
  • Exomes 𝑓: 0.013 (618 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.777

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]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-134820071-G-A is Benign according to our data. Variant chr9-134820071-G-A is described in ClinVar as [Benign]. Clinvar id is 255088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.4447-45G>A		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.4447-45G>A		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.4447-45G>A		intron_variant			XP_016869755.1
LOC101448202	NR_103451.2	n.209C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.4447-45G>A		intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.4447-45G>A		intron_variant		2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6702 AN: 152166 Hom.: 395 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.0349

GnomAD3 exomes AF: 0.0225 AC: 5647 AN: 250446 Hom.: 249 AF XY: 0.0200 AC XY: 2714 AN XY: 135514

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.0902

Gnomad SAS exome AF: 0.0200

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00409

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.0126 AC: 16568 AN: 1310730 Hom.: 618 Cov.: 20 AF XY: 0.0123 AC XY: 8102 AN XY: 660338

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.000832

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.00130

Gnomad4 NFE exome AF: 0.00480

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0441 AC: 6717 AN: 152286 Hom.: 399 Cov.: 33 AF XY: 0.0437 AC XY: 3250 AN XY: 74446

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0877

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0197 Hom.: 26

Bravo AF: 0.0502

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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	-0.87
CADD	Benign	0.21
DANN	Benign	0.78

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: rs3811147; hg19: chr9-137711917; COSMIC: COSV65670983; COSMIC: COSV65670983;