Genetic Variant FBLN1:p.Val10Val (chr22-45503015-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_006486.3(FBLN1):c.30C>T(p.Val10Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V10V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBLN1
NM_006486.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.332

Publications

0 publications found

Variant links:

Genes affected

FBLN1 (HGNC:3600): (fibulin 1) Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [provided by RefSeq, Jul 2008]

FBLN1 Gene-Disease associations (from GenCC):

FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
synpolydactyly type 2
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

FBLN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.332 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006486.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FBLN1	NM_006486.3	MANE Select	c.30C>T	p.Val10Val	synonymous	Exon 1 of 17	NP_006477.3
FBLN1	NM_001996.4		c.30C>T	p.Val10Val	synonymous	Exon 1 of 15	NP_001987.3
FBLN1	NM_006485.4		c.30C>T	p.Val10Val	synonymous	Exon 1 of 15	NP_006476.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBLN1	ENST00000327858.11	TSL:1 MANE Select	c.30C>T	p.Val10Val	synonymous	Exon 1 of 17	ENSP00000331544.6	P23142-1
FBLN1	ENST00000262722.11	TSL:1	c.30C>T	p.Val10Val	synonymous	Exon 1 of 15	ENSP00000262722.7	P23142-4
FBLN1	ENST00000442170.6	TSL:1	c.30C>T	p.Val10Val	synonymous	Exon 1 of 15	ENSP00000393812.2	P23142-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1094084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

524496

African (AFR)

AF:

0.00

AC:

AN:

22526

American (AMR)

AF:

0.00

AC:

AN:

9994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14458

East Asian (EAS)

AF:

0.00

AC:

AN:

25204

South Asian (SAS)

AF:

0.00

AC:

AN:

25308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2972

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

928574

Other (OTH)

AF:

0.00

AC:

AN:

43384

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

-0.33

PromoterAI

0.67

Over-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over