Variant chr5-128300793-C-T 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.6166+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 1,610,962 control chromosomes in the GnomAD database, including 8,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 612 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7539 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.135

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:

FBN2 (HGNC:):

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=-0.72).

BP6

Variant 5-128300793-C-T is Benign according to our data. Variant chr5-128300793-C-T is described in ClinVar as [Benign]. Clinvar id is 258521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.6166+24G>A		intron_variant		ENST00000262464.9	NP_001990.2	P35556-1
FBN2	XM_017009228.3 linkuse as main transcript	c.6013+24G>A		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.6166+24G>A	intron_variant	1	NM_001999.4	ENSP00000262464.4	P35556-1
FBN2	ENST00000703783.1 linkuse as main transcript	n.2950+24G>A	intron_variant
FBN2	ENST00000703785.1 linkuse as main transcript	n.2869+24G>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0826

AC:

12556

AN:

152046

Hom.:

612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0752

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0645

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0820

GnomAD3 exomes

AF:

0.0902

AC:

22681

AN:

251358

Hom.:

1068

AF XY:

0.0918

AC XY:

12474

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0596

Gnomad AMR exome

AF:

0.0873

Gnomad ASJ exome

AF:

0.0852

Gnomad EAS exome

AF:

0.0569

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0730

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0890

GnomAD4 exome

AF:

0.0995

AC:

145191

AN:

1458798

Hom.:

7539

Cov.:

AF XY:

0.100

AC XY:

72668

AN XY:

725904

show subpopulations

Gnomad4 AFR exome

AF:

0.0539

Gnomad4 AMR exome

AF:

0.0849

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.0614

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0703

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0983

GnomAD4 genome

AF:

0.0825

AC:

12554

AN:

152164

Hom.:

612

Cov.:

AF XY:

0.0802

AC XY:

5967

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0590

Gnomad4 AMR

AF:

0.0752

Gnomad4 ASJ

AF:

0.0812

Gnomad4 EAS

AF:

0.0593

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0645

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.0816

Alfa

AF:

0.0967

Hom.:

179

Bravo

AF:

0.0813

Asia WGS

AF:

0.0740

AC:

259

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

-0.72

CADD

Benign

4.6

DANN

Benign

0.74

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