5-128369178-C-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001999.4(FBN2):c.2248+4G>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
FBN2
NM_001999.4 splice_donor_region, intron
NM_001999.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001805
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.45
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.2248+4G>C | splice_donor_region_variant, intron_variant | ENST00000262464.9 | |||
FBN2 | XM_017009228.3 | c.2095+4G>C | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2248+4G>C | splice_donor_region_variant, intron_variant | 1 | NM_001999.4 | P1 | |||
FBN2 | ENST00000508989.5 | c.2149+4G>C | splice_donor_region_variant, intron_variant | 2 | |||||
FBN2 | ENST00000511489.1 | n.469+4G>C | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251276Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135792
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727204
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GnomAD4 genome Cov.: 32
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at