rs763404867
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001159699.2(FHL1):c.204+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,098,111 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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 Uncertain significance (★★).
Frequency
Consequence
NM_001159699.2 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.156+6G>A | splice_region_variant, intron_variant | ENST00000394155.8 | NP_001153174.1 | |||
FHL1 | NM_001159699.2 | c.204+6G>A | splice_region_variant, intron_variant | ENST00000370683.6 | NP_001153171.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.156+6G>A | splice_region_variant, intron_variant | 5 | NM_001159702.3 | ENSP00000377710.2 | ||||
FHL1 | ENST00000370683.6 | c.204+6G>A | splice_region_variant, intron_variant | 1 | NM_001159699.2 | ENSP00000359717.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 113016Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35168 FAILED QC
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183415Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67855
GnomAD4 exome AF: 0.00000637 AC: 7AN: 1098111Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 2AN XY: 363469
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 113016Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35168
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 10, 2023 | - - |
X-linked myopathy with postural muscle atrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2022 | This sequence change falls in intron 3 of the FHL1 gene. It does not directly change the encoded amino acid sequence of the FHL1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs763404867, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 537359). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at