dbSNP rs869097710: FBN2:c.5675-9delC (chr5-128305090-AG-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001999.4(FBN2):c.5675-9delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00892 in 1,569,628 control chromosomes in the GnomAD database, including 1,052 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 571 hom., cov: 31)

Exomes 𝑓: 0.0049 ( 481 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.918

Publications

3 publications found

Variant links:

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

FBN2 Gene-Disease associations (from GenCC):

congenital contractural arachnodactyly
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
carpal tunnel syndrome
Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
macular degeneration, early-onset
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial thoracic aortic aneurysm and aortic dissection
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

FBN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 5-128305090-AG-A is Benign according to our data. Variant chr5-128305090-AG-A is described in ClinVar as Benign. ClinVar VariationId is 213239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN2	NM_001999.4	MANE Select	c.5675-9delC		intron	N/A	NP_001990.2	P35556-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBN2	ENST00000262464.9	TSL:1 MANE Select	c.5675-9delC	intron	N/A	ENSP00000262464.4	P35556-1
FBN2	ENST00000939405.1		c.5576-9delC	intron	N/A	ENSP00000609464.1
FBN2	ENST00000939404.1		c.5522-9delC	intron	N/A	ENSP00000609463.1

Frequencies

GnomAD3 genomes

AF:

0.0463

AC:

7022

AN:

151574

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.0370

GnomAD2 exomes

AF:

0.0152

AC:

2933

AN:

192500

AF XY:

0.0113

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.000256

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.00729

GnomAD4 exome

AF:

0.00490

AC:

6952

AN:

1417940

Hom.:

481

Cov.:

AF XY:

0.00422

AC XY:

2979

AN XY:

706216

show subpopulations

African (AFR)

AF:

0.159

AC:

5182

AN:

32626

American (AMR)

AF:

0.0110

AC:

477

AN:

43172

Ashkenazi Jewish (ASJ)

AF:

0.000156

AC:

AN:

25614

East Asian (EAS)

AF:

0.00144

AC:

AN:

38832

South Asian (SAS)

AF:

0.000511

AC:

AN:

84122

European-Finnish (FIN)

AF:

0.0000759

AC:

AN:

52670

Middle Eastern (MID)

AF:

0.00602

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000459

AC:

494

AN:

1076414

Other (OTH)

AF:

0.0112

AC:

658

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

295

590

886

1181

1476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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:

0.0464

AC:

7043

AN:

151688

Hom.:

571

Cov.:

AF XY:

0.0459

AC XY:

3405

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.161

AC:

6636

AN:

41276

American (AMR)

AF:

0.0187

AC:

285

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00136

AC:

AN:

5152

South Asian (SAS)

AF:

0.00104

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000427

AC:

AN:

67906

Other (OTH)

AF:

0.0366

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

288

576

863

1151

1439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.00361

Hom.:

Bravo

AF:

0.0515

Asia WGS

AF:

0.00838

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Congenital contractural arachnodactyly (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.92

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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