chrX-154353466-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001110556.2(FLNA):​c.5861-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,112 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000018 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

FLNA
NM_001110556.2 intron

Scores

2
Splicing: ADA: 0.00003060
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0950

Publications

0 publications found
Variant links:
Genes affected
FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
FLNA Gene-Disease associations (from GenCC):
  • periventricular nodular heterotopia
    Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • frontometaphyseal dysplasia 1
    Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
  • genetic developmental and epileptic encephalopathy
    Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
  • heterotopia, periventricular, X-linked dominant
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
  • intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • Melnick-Needles syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
  • otopalatodigital syndrome type 2
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
  • terminal osseous dysplasia-pigmentary defects syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
  • cardiac valvular dysplasia, X-linked
    Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • frontometaphyseal dysplasia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital short bowel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • otopalatodigital syndrome type 1
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked Ehlers-Danlos syndrome
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • familial thoracic aortic aneurysm and aortic dissection
    Inheritance: XL Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant X-154353466-G-A is Benign according to our data. Variant chrX-154353466-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465004.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL,AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLNANM_001110556.2 linkc.5861-9C>T intron_variant Intron 36 of 47 ENST00000369850.10 NP_001104026.1 P21333-1Q60FE5Q6NXF2
FLNANM_001456.4 linkc.5837-9C>T intron_variant Intron 35 of 46 NP_001447.2 P21333-2Q60FE5Q6NXF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLNAENST00000369850.10 linkc.5861-9C>T intron_variant Intron 36 of 47 1 NM_001110556.2 ENSP00000358866.3 P21333-1

Frequencies

GnomAD3 genomes
AF:
0.0000177
AC:
2
AN:
112744
Hom.:
0
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000376
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000110
AC:
2
AN:
181516
AF XY:
0.0000148
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.000224
GnomAD4 exome
AF:
0.00000365
AC:
4
AN:
1097368
Hom.:
0
Cov.:
32
AF XY:
0.00000551
AC XY:
2
AN XY:
363134
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26402
American (AMR)
AF:
0.00
AC:
0
AN:
35205
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19384
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30206
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54143
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
39866
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
0.00000356
AC:
3
AN:
841943
Other (OTH)
AF:
0.0000217
AC:
1
AN:
46082
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
AF:
0.0000177
AC:
2
AN:
112744
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34880
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31020
American (AMR)
AF:
0.00
AC:
0
AN:
10764
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2656
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3614
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2770
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6264
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
0.0000376
AC:
2
AN:
53214
Other (OTH)
AF:
0.00
AC:
0
AN:
1520
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000868
Hom.:
1
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
May 27, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.5
DANN
Benign
0.37
PhyloP100
0.095
PromoterAI
0.0086
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000031
dbscSNV1_RF
Benign
0.010
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs782153045; hg19: chrX-153581834; API