9-134732515-C-G

Variant names:

• chr9-134732515-C-G
• rs3124311
• NM_000093.5:c.1389+388C>G

Variant summary

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

The NM_000093.5(COL5A1):​c.1389+388C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 373,570 control chromosomes in the GnomAD database, including 48,622 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 0.46 (17414 hom., cov: 33)
  • Exomes 𝑓: 0.52 (31208 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 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.1389+388C>G		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.1389+388C>G		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.1389+388C>G		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000469093.1	TSL:3	n.516C>G		non_coding_transcript_exon	Exon 2 of 2
	COL5A1	ENST00000371820.4	TSL:2	c.1389+388C>G		intron	N/A	ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69977 AN: 151908 Hom.: 17396 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.524 AC: 116170 AN: 221544 Hom.: 31208 Cov.: 0 AF XY: 0.532 AC XY: 61527 AN XY: 115606

African (AFR) AF: 0.271 AC: 2058 AN: 7600

American (AMR) AF: 0.686 AC: 6554 AN: 9560

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 4539 AN: 6542

East Asian (EAS) AF: 0.477 AC: 6154 AN: 12910

South Asian (SAS) AF: 0.629 AC: 17679 AN: 28100

European-Finnish (FIN) AF: 0.511 AC: 6067 AN: 11878

Middle Eastern (MID) AF: 0.596 AC: 559 AN: 938

European-Non Finnish (NFE) AF: 0.502 AC: 65950 AN: 131348

Other (OTH) AF: 0.522 AC: 6610 AN: 12668

GnomAD4 genome AF: 0.461 AC: 70026 AN: 152026 Hom.: 17414 Cov.: 33 AF XY: 0.469 AC XY: 34833 AN XY: 74284

African (AFR) AF: 0.275 AC: 11413 AN: 41446

American (AMR) AF: 0.622 AC: 9504 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2378 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2506 AN: 5164

South Asian (SAS) AF: 0.644 AC: 3106 AN: 4820

European-Finnish (FIN) AF: 0.509 AC: 5373 AN: 10552

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34122 AN: 67970

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.309 Hom.: 793

Bravo AF: 0.457

Asia WGS AF: 0.592 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.77
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: rs3124311; hg19: chr9-137624361;