NM_000093.5:c.278-3987G>A

Variant names:

• chr9-134695922-G-A
• rs4841924
• NM_000093.5:c.278-3987G>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.278-3987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,076 control chromosomes in the GnomAD database, including 55,289 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 0.84 (55289 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.278-3987G>A		intron_variant	Intron 2 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.278-3987G>A		intron_variant	Intron 2 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.278-3987G>A		intron_variant	Intron 2 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.278-3987G>A		intron_variant	Intron 2 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.278-3987G>A		intron_variant	Intron 2 of 65	2		ENSP00000360885.4
COL5A1	ENST00000464187.1	n.700-3987G>A		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128252 AN: 151958 Hom.: 55256 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.844 AC: 128339 AN: 152076 Hom.: 55289 Cov.: 32 AF XY: 0.844 AC XY: 62709 AN XY: 74318

African (AFR) AF: 0.650 AC: 26965 AN: 41458

American (AMR) AF: 0.905 AC: 13854 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3185 AN: 3468

East Asian (EAS) AF: 0.977 AC: 5020 AN: 5136

South Asian (SAS) AF: 0.874 AC: 4187 AN: 4792

European-Finnish (FIN) AF: 0.853 AC: 9042 AN: 10604

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63227 AN: 67996

Other (OTH) AF: 0.853 AC: 1803 AN: 2114

Alfa AF: 0.905 Hom.: 70644

Bravo AF: 0.839

Asia WGS AF: 0.895 AC: 3107 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.79
DANN	Benign	0.39
PhyloP100		-0.98
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: rs4841924; hg19: chr9-137587768;