rs4842161

Variant names:

• chr9-134767842-C-A
• rs4842161
• NM_000093.5:c.2232+488C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000093.5(COL5A1):​c.2232+488C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,050 control chromosomes in the GnomAD database, including 31,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (31046 hom., cov: 33)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 4 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: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.2232+488C>A		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.2232+488C>A		intron	N/A	NP_001265003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.2232+488C>A		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000371820.4	TSL:2	c.2232+488C>A		intron	N/A	ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94082 AN: 151930 Hom.: 31002 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.619 AC: 94181 AN: 152050 Hom.: 31046 Cov.: 33 AF XY: 0.615 AC XY: 45735 AN XY: 74310

African (AFR) AF: 0.844 AC: 34996 AN: 41480

American (AMR) AF: 0.496 AC: 7591 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3468

East Asian (EAS) AF: 0.882 AC: 4557 AN: 5164

South Asian (SAS) AF: 0.519 AC: 2499 AN: 4814

European-Finnish (FIN) AF: 0.520 AC: 5491 AN: 10558

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

European-Non Finnish (NFE) AF: 0.528 AC: 35886 AN: 67962

Other (OTH) AF: 0.569 AC: 1199 AN: 2106

Alfa AF: 0.539 Hom.: 37952

Bravo AF: 0.629

Asia WGS AF: 0.702 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.031
DANN	Benign	0.51
PhyloP100		-2.6
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: rs4842161; hg19: chr9-137659688;