rs774024150
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001159699.2(FHL1):c.852G>A(p.Gln284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,243 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000091 ( 0 hom. 3 hem. )
Consequence
FHL1
NM_001159699.2 synonymous
NM_001159699.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.860
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant X-136209986-G-A is Benign according to our data. Variant chrX-136209986-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1695317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.86 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL1 | NM_001159699.2 | c.852G>A | p.Gln284= | synonymous_variant | 6/6 | ENST00000370683.6 | |
FHL1 | NM_001159702.3 | c.*32G>A | 3_prime_UTR_variant | 8/8 | ENST00000394155.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000370683.6 | c.852G>A | p.Gln284= | synonymous_variant | 6/6 | 1 | NM_001159699.2 | P1 | |
FHL1 | ENST00000394155.8 | c.*32G>A | 3_prime_UTR_variant | 8/8 | 5 | NM_001159702.3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
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22
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183531Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67959
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GnomAD4 exome AF: 0.00000911 AC: 10AN: 1098243Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 3AN XY: 363597
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GnomAD4 genome ? Cov.: 22
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
X-linked myopathy with postural muscle atrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2022 | 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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at