Variant 5-128350042-G-T 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.2813-37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,523,168 control chromosomes in the GnomAD database, including 862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 62 hom., cov: 33)

Exomes 𝑓: 0.032 ( 800 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0510

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=-0.87).

BP6

Variant 5-128350042-G-T is Benign according to our data. Variant chr5-128350042-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 258513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3301/152212) while in subpopulation NFE AF= 0.0367 (2495/68012). AF 95% confidence interval is 0.0355. There are 62 homozygotes in gnomad4. There are 1488 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.2813-37C>A		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3 linkuse as main transcript	c.2660-37C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.2813-37C>A		intron_variant		1	NM_001999.4	P1	P35556-1
FBN2	ENST00000508989.5 linkuse as main transcript	c.2714-37C>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3305

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00645

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00906

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0234

AC:

5868

AN:

250322

Hom.:

105

AF XY:

0.0247

AC XY:

3346

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.00613

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0186

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0324

AC:

44484

AN:

1370956

Hom.:

800

Cov.:

AF XY:

0.0320

AC XY:

21996

AN XY:

687358

show subpopulations

Gnomad4 AFR exome

AF:

0.00492

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0304

GnomAD4 genome

AF:

0.0217

AC:

3301

AN:

152212

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1488

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00640

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.00906

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0258

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00635

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 26, 2018	- -
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

-0.87

CADD

Benign

1.8

DANN

Benign

0.40

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