chrX-136209862-TC-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001159699.2(FHL1):c.737-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,162,380 control chromosomes in the GnomAD database, including 1 homozygotes. There are 168 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., 33 hem., cov: 20)
Exomes 𝑓: 0.00057 ( 1 hom. 135 hem. )
Consequence
FHL1
NM_001159699.2 splice_region, intron
NM_001159699.2 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.111
Genes affected
FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant X-136209862-TC-T is Benign according to our data. Variant chrX-136209862-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 198465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136209862-TC-T is described in Lovd as [Likely_benign]. Variant chrX-136209862-TC-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00147 (161/109191) while in subpopulation AFR AF= 0.00432 (130/30082). AF 95% confidence interval is 0.00372. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 33 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.889-3delC | splice_region_variant, intron_variant | ENST00000394155.8 | NP_001153174.1 | |||
FHL1 | NM_001159699.2 | c.737-3delC | 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.889-3delC | splice_region_variant, intron_variant | 5 | NM_001159702.3 | ENSP00000377710.2 | ||||
FHL1 | ENST00000370683.6 | c.737-3delC | splice_region_variant, intron_variant | 1 | NM_001159699.2 | ENSP00000359717.1 |
Frequencies
GnomAD3 genomes AF: 0.00147 AC: 160AN: 109147Hom.: 0 Cov.: 20 AF XY: 0.00101 AC XY: 32AN XY: 31665
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GnomAD3 exomes AF: 0.00130 AC: 219AN: 168269Hom.: 1 AF XY: 0.000498 AC XY: 29AN XY: 58243
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GnomAD4 exome AF: 0.000572 AC: 602AN: 1053189Hom.: 1 Cov.: 32 AF XY: 0.000398 AC XY: 135AN XY: 339267
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GnomAD4 genome AF: 0.00147 AC: 161AN: 109191Hom.: 0 Cov.: 20 AF XY: 0.00104 AC XY: 33AN XY: 31721
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 07, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 13, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2016 | - - |
X-linked myopathy with postural muscle atrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 28, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at