rs73074072
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001457.4(FLNB):c.1611-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,978 control chromosomes in the GnomAD database, including 3,403 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001457.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNB | NM_001457.4 | c.1611-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000295956.9 | |||
FLNB | NM_001164317.2 | c.1611-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
FLNB | NM_001164318.2 | c.1611-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
FLNB | NM_001164319.2 | c.1611-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNB | ENST00000295956.9 | c.1611-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001457.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0410 AC: 6242AN: 152184Hom.: 172 Cov.: 32
GnomAD3 exomes AF: 0.0445 AC: 11200AN: 251480Hom.: 366 AF XY: 0.0455 AC XY: 6181AN XY: 135912
GnomAD4 exome AF: 0.0619 AC: 90538AN: 1461676Hom.: 3231 Cov.: 32 AF XY: 0.0610 AC XY: 44348AN XY: 727142
GnomAD4 genome ? AF: 0.0410 AC: 6242AN: 152302Hom.: 172 Cov.: 32 AF XY: 0.0394 AC XY: 2932AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2016 | 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 07, 2023 | - - |
FLNB-Related Spectrum Disorders Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Connective tissue disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at