Variant 5-128289088-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001999.4(FBN2):c.6637+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,610,364 control chromosomes in the GnomAD database, including 1,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 83 hom., cov: 32)

Exomes 𝑓: 0.034 ( 995 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.38

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 5-128289088-T-C is Benign according to our data. Variant chr5-128289088-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-128289088-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0281 (4278/152246) while in subpopulation AMR AF= 0.0415 (634/15280). AF 95% confidence interval is 0.0392. There are 83 homozygotes in gnomad4. There are 2038 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.6637+39A>G		intron_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3 linkuse as main transcript	c.6484+39A>G		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.6637+39A>G	intron_variant	1	NM_001999.4	ENSP00000262464	P1	P35556-1
FBN2	ENST00000703783.1 linkuse as main transcript	n.3421+39A>G	intron_variant, non_coding_transcript_variant
FBN2	ENST00000703785.1 linkuse as main transcript	n.3340+39A>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4279

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0405

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0278

AC:

6948

AN:

249988

Hom.:

151

AF XY:

0.0281

AC XY:

3804

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00663

Gnomad AMR exome

AF:

0.0214

Gnomad ASJ exome

AF:

0.00858

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00739

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0378

GnomAD4 exome

AF:

0.0339

AC:

49491

AN:

1458118

Hom.:

995

Cov.:

AF XY:

0.0333

AC XY:

24201

AN XY:

725682

show subpopulations

Gnomad4 AFR exome

AF:

0.00587

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.00796

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00746

Gnomad4 FIN exome

AF:

0.0447

Gnomad4 NFE exome

AF:

0.0389

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0281

AC:

4278

AN:

152246

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2038

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00763

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0397

Gnomad4 NFE

AF:

0.0405

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0274

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0030

DANN

Benign

0.65

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