rs3811161

Variant names:

• chr9-134796731-A-G
• rs3811161
• NM_000093.5:c.2845-117A>G

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.2845-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 987,228 control chromosomes in the GnomAD database, including 132,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20867 hom., cov: 32)
  • Exomes 𝑓: 0.51 (111401 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.78
• Publications: 5 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: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 9-134796731-A-G is Benign according to our data. Variant chr9-134796731-A-G is described in ClinVar as Benign. ClinVar VariationId is 672276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.2845-117A>G		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.2845-117A>G		intron	N/A	NP_001265003.1	P20908-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.2845-117A>G		intron	N/A	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.2845-117A>G		intron	N/A	ENSP00000360885.4	P20908-2
	COL5A1	ENST00000950240.1		c.2836-117A>G		intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79047 AN: 151924 Hom.: 20852 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.512 AC: 427645 AN: 835186 Hom.: 111401 AF XY: 0.513 AC XY: 225492 AN XY: 439414

African (AFR) AF: 0.573 AC: 12330 AN: 21530

American (AMR) AF: 0.466 AC: 19372 AN: 41562

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 11738 AN: 21888

East Asian (EAS) AF: 0.762 AC: 27968 AN: 36720

South Asian (SAS) AF: 0.545 AC: 39597 AN: 72654

European-Finnish (FIN) AF: 0.456 AC: 23415 AN: 51298

Middle Eastern (MID) AF: 0.532 AC: 2239 AN: 4206

European-Non Finnish (NFE) AF: 0.495 AC: 270262 AN: 545594

Other (OTH) AF: 0.522 AC: 20724 AN: 39734

GnomAD4 genome AF: 0.520 AC: 79113 AN: 152042 Hom.: 20867 Cov.: 32 AF XY: 0.518 AC XY: 38531 AN XY: 74314

African (AFR) AF: 0.571 AC: 23688 AN: 41462

American (AMR) AF: 0.450 AC: 6874 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3982 AN: 5154

South Asian (SAS) AF: 0.551 AC: 2655 AN: 4820

European-Finnish (FIN) AF: 0.458 AC: 4848 AN: 10590

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33696 AN: 67948

Other (OTH) AF: 0.511 AC: 1078 AN: 2108

Alfa AF: 0.517 Hom.: 2675

Bravo AF: 0.523

Asia WGS AF: 0.653 AC: 2268 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.20
PhyloP100		-2.8
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: rs3811161; hg19: chr9-137688577; COSMIC: COSV65667152;