Variant rs10519991 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.2429-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,576,632 control chromosomes in the GnomAD database, including 6,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 448 hom., cov: 32)

Exomes 𝑓: 0.089 ( 5946 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0880

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=-0.88).

BP6

Variant 5-128361896-A-G is Benign according to our data. Variant chr5-128361896-A-G is described in ClinVar as [Benign]. Clinvar id is 258512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0934 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.2429-48T>C		intron_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3 linkuse as main transcript	c.2276-48T>C		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.2429-48T>C		intron_variant		1	NM_001999.4	ENSP00000262464	P1	P35556-1
FBN2	ENST00000508989.5 linkuse as main transcript	c.2330-48T>C		intron_variant		2		ENSP00000425596

Frequencies

GnomAD3 genomes

AF:

0.0680

AC:

10349

AN:

152150

Hom.:

449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.0540

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0643

Gnomad SAS

AF:

0.0494

Gnomad FIN

AF:

0.0944

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0954

Gnomad OTH

AF:

0.0679

GnomAD3 exomes

AF:

0.0729

AC:

18325

AN:

251232

Hom.:

778

AF XY:

0.0736

AC XY:

9998

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.0230

Gnomad AMR exome

AF:

0.0416

Gnomad ASJ exome

AF:

0.0454

Gnomad EAS exome

AF:

0.0582

Gnomad SAS exome

AF:

0.0448

Gnomad FIN exome

AF:

0.0954

Gnomad NFE exome

AF:

0.0976

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0885

AC:

126077

AN:

1424364

Hom.:

5946

Cov.:

AF XY:

0.0871

AC XY:

61932

AN XY:

711044

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.0508

Gnomad4 SAS exome

AF:

0.0456

Gnomad4 FIN exome

AF:

0.0954

Gnomad4 NFE exome

AF:

0.0981

Gnomad4 OTH exome

AF:

0.0838

GnomAD4 genome

AF:

0.0679

AC:

10344

AN:

152268

Hom.:

448

Cov.:

AF XY:

0.0663

AC XY:

4935

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0539

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.0642

Gnomad4 SAS

AF:

0.0488

Gnomad4 FIN

AF:

0.0944

Gnomad4 NFE

AF:

0.0953

Gnomad4 OTH

AF:

0.0676

Alfa

AF:

0.0849

Hom.:

362

Bravo

AF:

0.0644

Asia WGS

AF:

0.0640

AC:

221

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

-0.88

CADD

Benign

0.39

DANN

Benign

0.31

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