Variant rs17676694 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001999.4(FBN2):c.3343+35T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,611,170 control chromosomes in the GnomAD database, including 8,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 639 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8351 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0420

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-128344350-A-T is Benign according to our data. Variant chr5-128344350-A-T is described in ClinVar as [Benign]. Clinvar id is 258516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.3343+35T>A		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3 linkuse as main transcript	c.3190+35T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.3343+35T>A		intron_variant		1	NM_001999.4	P1	P35556-1
FBN2	ENST00000508989.5 linkuse as main transcript	c.3244+35T>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11525

AN:

152204

Hom.:

639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0830

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0660

GnomAD3 exomes

AF:

0.0772

AC:

19405

AN:

251286

Hom.:

960

AF XY:

0.0787

AC XY:

10688

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.0546

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0351

Gnomad FIN exome

AF:

0.0749

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.0917

GnomAD4 exome

AF:

0.101

AC:

147155

AN:

1458848

Hom.:

8351

Cov.:

AF XY:

0.0991

AC XY:

71959

AN XY:

725896

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0557

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0373

Gnomad4 FIN exome

AF:

0.0789

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.0844

GnomAD4 genome

AF:

0.0756

AC:

11523

AN:

152322

Hom.:

639

Cov.:

AF XY:

0.0716

AC XY:

5332

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.0829

Gnomad4 ASJ

AF:

0.0568

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.0296

Gnomad4 FIN

AF:

0.0695

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0653

Alfa

AF:

0.0909

Hom.:

145

Bravo

AF:

0.0730

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.3

DANN

Benign

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over