rs115237925

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_006329.4(FBLN5):c.*329T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0162 in 365,374 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 32)

Exomes 𝑓: 0.018 ( 162 hom. )

Consequence

FBLN5
NM_006329.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.47

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

cutis laxa, autosomal dominant 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp
cutis laxa, autosomal recessive, type 1A
Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
Charcot-Marie-Tooth disease, demyelinating, IIA 1H
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
demyelinating hereditary motor and sensory neuropathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
macular degeneration, age-related, 3
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
autosomal dominant cutis laxa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary sensorimotor neuropathy with hyperelastic skin
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive cutis laxa type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FBLN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-91869895-A-G is Benign according to our data. Variant chr14-91869895-A-G is described in ClinVar as Benign. ClinVar VariationId is 314868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006329.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBLN5	NM_006329.4	MANE Select	c.*329T>C	3_prime_UTR	Exon 11 of 11	NP_006320.2
FBLN5	NM_001384158.1		c.*329T>C	3_prime_UTR	Exon 12 of 12	NP_001371087.1	G3XA98
FBLN5	NM_001384159.1		c.*329T>C	3_prime_UTR	Exon 11 of 11	NP_001371088.1	G3V4U0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBLN5	ENST00000342058.9	TSL:1 MANE Select	c.*329T>C	3_prime_UTR	Exon 11 of 11	ENSP00000345008.4	Q9UBX5
FBLN5	ENST00000267620.14	TSL:1	c.*329T>C	3_prime_UTR	Exon 12 of 12	ENSP00000267620.10	G3XA98
FBLN5	ENST00000706676.1		c.*329T>C	3_prime_UTR	Exon 12 of 12	ENSP00000516492.1	A0A9L9PY85

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2086

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0269

Gnomad SAS

AF:

0.0765

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00860

GnomAD4 exome

AF:

0.0179

AC:

3824

AN:

213098

Hom.:

162

Cov.:

AF XY:

0.0244

AC XY:

2830

AN XY:

116028

show subpopulations

African (AFR)

AF:

0.0322

AC:

188

AN:

5840

American (AMR)

AF:

0.00254

AC:

AN:

11410

Ashkenazi Jewish (ASJ)

AF:

0.000196

AC:

AN:

5100

East Asian (EAS)

AF:

0.0261

AC:

239

AN:

9172

South Asian (SAS)

AF:

0.0760

AC:

3147

AN:

41430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9434

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

736

European-Non Finnish (NFE)

AF:

0.000796

AC:

AN:

119402

Other (OTH)

AF:

0.0113

AC:

119

AN:

10574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

170

340

511

681

851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.0138

AC:

2104

AN:

152276

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0339

AC:

1407

AN:

41534

American (AMR)

AF:

0.00549

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.0270

AC:

140

AN:

5184

South Asian (SAS)

AF:

0.0769

AC:

371

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68026

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00986

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0570

AC:

201

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cutis laxa (1)

Macular degeneration, age-related, 3 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

5.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over