GeneBe

X-136169520-GAA-GAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000543669.5(FHL1):​c.-478dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 18535 hom., 18546 hem., cov: 0)
Exomes 𝑓: 0.65 ( 13909 hom. 15785 hem. )
Failed GnomAD Quality Control

Consequence

FHL1
ENST00000543669.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0940

Publications

1 publications found
Variant links:
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]
FHL1 Gene-Disease associations (from GenCC):
  • X-linked myopathy with postural muscle atrophy
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
  • myopathy, reducing body, X-linked, early-onset, severe
    Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • reducing body myopathy
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked Emery-Dreifuss muscular dystrophy
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked scapuloperoneal muscular dystrophy
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6
Variant X-136169520-G-GA is Benign according to our data. Variant chrX-136169520-G-GA is described in ClinVar as [Benign]. Clinvar id is 1249824.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHL1NM_001159702.3 linkc.-100-378dupA intron_variant Intron 1 of 7 ENST00000394155.8 NP_001153174.1 Q13642-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FHL1ENST00000394155.8 linkc.-100-378dupA intron_variant Intron 1 of 7 5 NM_001159702.3 ENSP00000377710.2 Q13642-2

Frequencies

GnomAD3 genomes
AF:
0.676
AC:
71059
AN:
105060
Hom.:
18535
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.491
Gnomad AMI
AF:
0.733
Gnomad AMR
AF:
0.665
Gnomad ASJ
AF:
0.657
Gnomad EAS
AF:
0.601
Gnomad SAS
AF:
0.637
Gnomad FIN
AF:
0.794
Gnomad MID
AF:
0.639
Gnomad NFE
AF:
0.781
Gnomad OTH
AF:
0.640
GnomAD4 exome
AF:
0.653
AC:
59462
AN:
91100
Hom.:
13909
Cov.:
0
AF XY:
0.615
AC XY:
15785
AN XY:
25686
show subpopulations
African (AFR)
AF:
0.404
AC:
1216
AN:
3012
American (AMR)
AF:
0.596
AC:
2727
AN:
4578
Ashkenazi Jewish (ASJ)
AF:
0.586
AC:
1338
AN:
2285
East Asian (EAS)
AF:
0.519
AC:
2165
AN:
4172
South Asian (SAS)
AF:
0.573
AC:
7203
AN:
12566
European-Finnish (FIN)
AF:
0.736
AC:
3097
AN:
4207
Middle Eastern (MID)
AF:
0.557
AC:
182
AN:
327
European-Non Finnish (NFE)
AF:
0.697
AC:
38504
AN:
55242
Other (OTH)
AF:
0.643
AC:
3030
AN:
4711
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
0
590
1180
1771
2361
2951
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
234
468
702
936
1170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.676
AC:
71066
AN:
105096
Hom.:
18535
Cov.:
0
AF XY:
0.660
AC XY:
18546
AN XY:
28086
show subpopulations
African (AFR)
AF:
0.491
AC:
14289
AN:
29102
American (AMR)
AF:
0.666
AC:
6477
AN:
9731
Ashkenazi Jewish (ASJ)
AF:
0.657
AC:
1681
AN:
2559
East Asian (EAS)
AF:
0.600
AC:
1983
AN:
3304
South Asian (SAS)
AF:
0.639
AC:
1461
AN:
2287
European-Finnish (FIN)
AF:
0.794
AC:
3624
AN:
4563
Middle Eastern (MID)
AF:
0.615
AC:
126
AN:
205
European-Non Finnish (NFE)
AF:
0.781
AC:
40025
AN:
51247
Other (OTH)
AF:
0.637
AC:
914
AN:
1435
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
740
1481
2221
2962
3702
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
602
1204
1806
2408
3010
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.530
Hom.:
1688

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 08, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.094
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs397710404; hg19: chrX-135251679; COSMIC: COSV61779502; COSMIC: COSV61779502; API