Variant 14-91869710-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006329.4(FBLN5):c.*514A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 162,658 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., cov: 32)

Exomes 𝑓: 0.019 ( 2 hom. )

Consequence

FBLN5
NM_006329.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.67

Variant links:

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]

FBLN5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-91869710-T-C is Benign according to our data. Variant chr14-91869710-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 314864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2535/152324) while in subpopulation NFE AF= 0.026 (1766/68032). AF 95% confidence interval is 0.0249. There are 35 homozygotes in gnomad4. There are 1175 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN5	NM_006329.4 linkuse as main transcript	c.*514A>G		3_prime_UTR_variant	11/11	ENST00000342058.9	NP_006320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN5	ENST00000342058.9 linkuse as main transcript	c.*514A>G		3_prime_UTR_variant	11/11	1	NM_006329.4	ENSP00000345008	P1

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2532

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0165

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.0187

AC:

193

AN:

10334

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

AN XY:

5290

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.00725

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00495

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0248

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0166

AC:

2535

AN:

152324

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1175

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Macular degeneration, age-related, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

- -

Cutis laxa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over