Genetic Variant FBLN2:p.Asp1204Asp (chr3-13637835-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001004019.2(FBLN2):c.3612C>T(p.Asp1204Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,034 control chromosomes in the GnomAD database, including 97,526 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 0.41 ( 14326 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83200 hom. )

Consequence

FBLN2
NM_001004019.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

FBLN2 (HGNC:3601): (fibulin 2) This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FBLN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN2	NM_001004019.2 link	c.3612C>T	p.Asp1204Asp	synonymous_variant	Exon 18 of 18	ENST00000404922.8	NP_001004019.1	P98095-2Q9Y3V7Q86V58
FBLN2	NM_001165035.2 link	c.3612C>T	p.Asp1204Asp	synonymous_variant	Exon 18 of 18		NP_001158507.1	P98095-2Q9Y3V7Q86V58
FBLN2	NM_001998.3 link	c.3471C>T	p.Asp1157Asp	synonymous_variant	Exon 17 of 17		NP_001989.2	P98095-1Q9Y3V7Q86V58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8 link	c.3612C>T	p.Asp1204Asp	synonymous_variant	Exon 18 of 18	5	NM_001004019.2	ENSP00000384169.3		P98095-2

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62227

AN:

151978

Hom.:

14301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.396

GnomAD3 exomes

AF:

0.370

AC:

91892

AN:

248504

Hom.:

18669

AF XY:

0.362

AC XY:

48841

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.675

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.329

AC:

480009

AN:

1460938

Hom.:

83200

Cov.:

AF XY:

0.328

AC XY:

238582

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.621

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.410

AC:

62301

AN:

152096

Hom.:

14326

Cov.:

AF XY:

0.409

AC XY:

30418

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.602

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.661

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.337

Hom.:

18338

Bravo

AF:

0.430

Asia WGS

AF:

0.514

AC:

1786

AN:

3478

EpiCase

AF:

0.326

EpiControl

AF:

0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

6.2

DANN

Benign

0.60

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over