chrX-136196860-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001159702.3(FHL1):c.-26-9547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,163,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., 18 hem., cov: 23)
Exomes 𝑓: 0.00016 ( 0 hom. 48 hem. )
Consequence
FHL1
NM_001159702.3 intron
NM_001159702.3 intron
Scores
1
12
Clinical Significance
Conservation
PhyloP100: 1.10
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.008448601).
BP6
Variant X-136196860-G-A is Benign according to our data. Variant chrX-136196860-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 993975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00035 (39/111409) while in subpopulation AMR AF= 0.00171 (18/10496). AF 95% confidence interval is 0.00111. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 18 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.-26-9547G>A | intron_variant | ENST00000394155.8 | NP_001153174.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.-26-9547G>A | intron_variant | 5 | NM_001159702.3 | ENSP00000377710 |
Frequencies
GnomAD3 genomes AF: 0.000350 AC: 39AN: 111355Hom.: 0 Cov.: 23 AF XY: 0.000536 AC XY: 18AN XY: 33569
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GnomAD3 exomes AF: 0.000990 AC: 112AN: 113170Hom.: 0 AF XY: 0.000693 AC XY: 28AN XY: 40404
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GnomAD4 exome AF: 0.000162 AC: 170AN: 1051829Hom.: 0 Cov.: 29 AF XY: 0.000140 AC XY: 48AN XY: 342801
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GnomAD4 genome AF: 0.000350 AC: 39AN: 111409Hom.: 0 Cov.: 23 AF XY: 0.000535 AC XY: 18AN XY: 33633
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 27, 2021 | - - |
FHL1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 02, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
GERP RS
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