NM_006486.3:c.152C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006486.3(FBLN1):c.152C>T(p.Ser51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FBLN1
NM_006486.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.88

Publications

2 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: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

FBLN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24786243).

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.152C>T	p.Ser51Leu	missense	Exon 2 of 17	NP_006477.3
FBLN1	NM_001996.4		c.152C>T	p.Ser51Leu	missense	Exon 2 of 15	NP_001987.3
FBLN1	NM_006485.4		c.152C>T	p.Ser51Leu	missense	Exon 2 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.152C>T	p.Ser51Leu	missense	Exon 2 of 17	ENSP00000331544.6	P23142-1
FBLN1	ENST00000262722.11	TSL:1	c.152C>T	p.Ser51Leu	missense	Exon 2 of 15	ENSP00000262722.7	P23142-4
FBLN1	ENST00000442170.6	TSL:1	c.152C>T	p.Ser51Leu	missense	Exon 2 of 15	ENSP00000393812.2	P23142-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000325

AC:

AN:

246260

AF XY:

0.0000525

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1459920

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726042

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000817

AC:

AN:

85650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111214

Other (OTH)

AF:

0.0000166

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

-0.12

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.019

MutationAssessor

Benign

1.4

PhyloP100

2.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.082

Vest4

0.43

MutPred

0.44

Gain of catalytic residue at S51 (P = 5e-04)

MVP

0.96

MPC

1.0

ClinPred

0.20

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.094

gMVP

0.72

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over