5-128305169-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001999.4(FBN2):​c.5675-87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,132,668 control chromosomes in the GnomAD database, including 196,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 22235 hom., cov: 33)
Exomes 𝑓: 0.59 ( 174468 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.51
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 5-128305169-A-G is Benign according to our data. Variant chr5-128305169-A-G is described in ClinVar as [Benign]. Clinvar id is 671004.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBN2NM_001999.4 linkc.5675-87T>C intron_variant Intron 44 of 64 ENST00000262464.9 NP_001990.2 P35556-1
FBN2XM_017009228.3 linkc.5522-87T>C intron_variant Intron 43 of 63 XP_016864717.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBN2ENST00000262464.9 linkc.5675-87T>C intron_variant Intron 44 of 64 1 NM_001999.4 ENSP00000262464.4 P35556-1
FBN2ENST00000703783.1 linkn.2459-87T>C intron_variant Intron 19 of 37
FBN2ENST00000703785.1 linkn.2378-87T>C intron_variant Intron 18 of 26

Frequencies

GnomAD3 genomes
AF:
0.502
AC:
76318
AN:
151976
Hom.:
22225
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.189
Gnomad AMI
AF:
0.558
Gnomad AMR
AF:
0.590
Gnomad ASJ
AF:
0.591
Gnomad EAS
AF:
0.805
Gnomad SAS
AF:
0.648
Gnomad FIN
AF:
0.711
Gnomad MID
AF:
0.601
Gnomad NFE
AF:
0.601
Gnomad OTH
AF:
0.520
GnomAD4 exome
AF:
0.588
AC:
576900
AN:
980574
Hom.:
174468
AF XY:
0.593
AC XY:
297342
AN XY:
501322
show subpopulations
Gnomad4 AFR exome
AF:
0.183
Gnomad4 AMR exome
AF:
0.578
Gnomad4 ASJ exome
AF:
0.596
Gnomad4 EAS exome
AF:
0.812
Gnomad4 SAS exome
AF:
0.645
Gnomad4 FIN exome
AF:
0.712
Gnomad4 NFE exome
AF:
0.579
Gnomad4 OTH exome
AF:
0.562
GnomAD4 genome
AF:
0.502
AC:
76341
AN:
152094
Hom.:
22235
Cov.:
33
AF XY:
0.513
AC XY:
38115
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.189
Gnomad4 AMR
AF:
0.590
Gnomad4 ASJ
AF:
0.591
Gnomad4 EAS
AF:
0.805
Gnomad4 SAS
AF:
0.649
Gnomad4 FIN
AF:
0.711
Gnomad4 NFE
AF:
0.601
Gnomad4 OTH
AF:
0.524
Alfa
AF:
0.592
Hom.:
57282
Bravo
AF:
0.472
Asia WGS
AF:
0.696
AC:
2416
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 14, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
15
DANN
Benign
0.79

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.

Other links and lift over

dbSNP: rs27855; hg19: chr5-127640861; API