chrX-136196863-G-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_001159702.3(FHL1):c.-26-9544G>T variant causes a intron change. The variant allele was found at a frequency of 0.0000146 in 1,163,229 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000081 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000076 ( 0 hom. 2 hem. )
Consequence
FHL1
NM_001159702.3 intron
NM_001159702.3 intron
Scores
4
2
7
Splicing: ADA: 0.9897
2
Clinical Significance
Conservation
PhyloP100: 6.34
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 -8 ACMG points.
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
Variant X-136196863-G-T is Benign according to our data. Variant chrX-136196863-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3036058.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000808 (9/111433) while in subpopulation AMR AF= 0.000286 (3/10488). AF 95% confidence interval is 0.0000774. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.-26-9544G>T | intron_variant | ENST00000394155.8 | NP_001153174.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.-26-9544G>T | intron_variant | 5 | NM_001159702.3 | ENSP00000377710 |
Frequencies
GnomAD3 genomes AF: 0.0000808 AC: 9AN: 111433Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33635
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GnomAD3 exomes AF: 0.0000530 AC: 6AN: 113237Hom.: 0 AF XY: 0.0000495 AC XY: 2AN XY: 40405
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GnomAD4 exome AF: 0.00000761 AC: 8AN: 1051796Hom.: 0 Cov.: 29 AF XY: 0.00000583 AC XY: 2AN XY: 342760
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GnomAD4 genome AF: 0.0000808 AC: 9AN: 111433Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33635
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
FHL1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2022 | This variant is classified as likely 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
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of disorder (P = 0.0062);
MVP
ClinPred
T
GERP RS
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at