Variant 14-91870431-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006329.4(FBLN5):c.1186-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,605,466 control chromosomes in the GnomAD database, including 187,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14925 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172677 hom. )

Consequence

FBLN5
NM_006329.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-91870431-T-C is Benign according to our data. Variant chr14-91870431-T-C is described in ClinVar as [Benign]. Clinvar id is 1227228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN5	NM_006329.4 linkuse as main transcript	c.1186-46A>G		intron_variant		ENST00000342058.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN5	ENST00000342058.9 linkuse as main transcript	c.1186-46A>G		intron_variant		1	NM_006329.4	P1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64866

AN:

152016

Hom.:

14911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.644

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.493

AC:

122732

AN:

248734

Hom.:

31162

AF XY:

0.499

AC XY:

67210

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.653

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.499

Gnomad NFE exome

AF:

0.489

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.484

AC:

703977

AN:

1453332

Hom.:

172677

Cov.:

AF XY:

0.487

AC XY:

352041

AN XY:

723338

show subpopulations

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.535

Gnomad4 EAS exome

AF:

0.638

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.498

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.489

GnomAD4 genome

AF:

0.427

AC:

64914

AN:

152134

Hom.:

14925

Cov.:

AF XY:

0.430

AC XY:

32026

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.256

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.535

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.506

Gnomad4 NFE

AF:

0.479

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.481

Hom.:

37629

Bravo

AF:

0.417

Asia WGS

AF:

0.532

AC:

1849

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.46

DANN

Benign

0.70

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

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