Variant rs42688 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.6758-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 1,608,032 control chromosomes in the GnomAD database, including 12,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2073 hom., cov: 32)

Exomes 𝑓: 0.071 ( 10591 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0300

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=-0.82).

BP6

Variant 5-128287478-A-G is Benign according to our data. Variant chr5-128287478-A-G is described in ClinVar as [Benign]. Clinvar id is 258524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 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.6758-48T>C		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3 linkuse as main transcript	c.6605-48T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.6758-48T>C		intron_variant		1	NM_001999.4	P1	P35556-1
FBN2	ENST00000703783.1 linkuse as main transcript	n.3542-48T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17710

AN:

152068

Hom.:

2070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0675

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0500

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0870

GnomAD3 exomes

AF:

0.112

AC:

27834

AN:

248304

Hom.:

4614

AF XY:

0.109

AC XY:

14681

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.0409

Gnomad ASJ exome

AF:

0.0563

Gnomad EAS exome

AF:

0.630

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0527

Gnomad NFE exome

AF:

0.0453

Gnomad OTH exome

AF:

0.0720

GnomAD4 exome

AF:

0.0706

AC:

102840

AN:

1455846

Hom.:

10591

Cov.:

AF XY:

0.0718

AC XY:

51979

AN XY:

724414

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.0417

Gnomad4 ASJ exome

AF:

0.0580

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0514

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0838

GnomAD4 genome

AF:

0.117

AC:

17735

AN:

152186

Hom.:

2073

Cov.:

AF XY:

0.121

AC XY:

9011

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.0672

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.601

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0500

Gnomad4 NFE

AF:

0.0457

Gnomad4 OTH

AF:

0.0894

Alfa

AF:

0.0664

Hom.:

200

Bravo

AF:

0.122

Asia WGS

AF:

0.313

AC:

1087

AN:

3476

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

-0.82

CADD

Benign

2.8

DANN

Benign

0.48

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