rs17732513

Positions:

• chr14-91920035-C-T

Variant summary

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

The NM_006329.4(FBLN5):​c.379+16912G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,044 control chromosomes in the GnomAD database, including 6,594 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 0.28 (6594 hom., cov: 32)
• Consequence: FBLN5 NM_006329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

FBLN5 (HGNC:3602): (fibulin 5) The protein encoded by this gene is a secreted, extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif and calcium-binding EGF-like domains. It promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. It is prominently expressed in developing arteries but less so in adult vessels. However, its expression is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells. Therefore, the protein encoded by this gene may play a role in vascular development and remodeling. Defects in this gene are a cause of autosomal dominant cutis laxa, autosomal recessive cutis laxa type I (CL type I), and age-related macular degeneration type 3 (ARMD3). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN5	NM_006329.4	c.379+16912G>A		intron_variant		ENST00000342058.9	NP_006320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN5	ENST00000342058.9	c.379+16912G>A		intron_variant		1	NM_006329.4	ENSP00000345008.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42253 AN: 151926 Hom.: 6590 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.278 AC: 42258 AN: 152044 Hom.: 6594 Cov.: 32 AF XY: 0.278 AC XY: 20679 AN XY: 74314

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.265

Alfa AF: 0.330 Hom.: 7971

Bravo AF: 0.265

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
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: rs17732513; hg19: chr14-92386379;