rs2287802

Positions:

• chr19-10002012-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015719.4(COL5A3):​c.850-131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 639,208 control chromosomes in the GnomAD database, including 48,441 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 0.37 (10590 hom., cov: 30)
  • Exomes 𝑓: 0.39 (37851 hom.)
• Consequence: COL5A3 NM_015719.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

Genes affected

COL5A3 (HGNC:14864): (collagen type V alpha 3 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. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A3	NM_015719.4	c.850-131T>C		intron_variant		ENST00000264828.4	NP_056534.2
COL5A3	XM_011528042.3	c.847-131T>C		intron_variant			XP_011526344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A3	ENST00000264828.4	c.850-131T>C		intron_variant		1	NM_015719.4	ENSP00000264828	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56277 AN: 151774 Hom.: 10576 Cov.: 30

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.389 AC: 189713 AN: 487316 Hom.: 37851 AF XY: 0.396 AC XY: 101389 AN XY: 256336

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.371 AC: 56328 AN: 151892 Hom.: 10590 Cov.: 30 AF XY: 0.374 AC XY: 27771 AN XY: 74216

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.371

Alfa AF: 0.380 Hom.: 15890

Bravo AF: 0.361

Asia WGS AF: 0.470 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.52
DANN	Benign	0.73

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: rs2287802; hg19: chr19-10112688;