NM_001110556.2:c.5861-9C>T
Variant names:
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
NM_001110556.2 intron
Scores
2
Splicing: ADA: 0.00003060
2
Clinical Significance
Conservation
PhyloP100: 0.0950
Publications
0 publications found
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 heterotopiaInheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- frontometaphyseal dysplasia 1Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
- genetic developmental and epileptic encephalopathyInheritance: XL Classification: DEFINITIVE Submitted by: G2P
- heterotopia, periventricular, X-linked dominantInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
- intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linkedInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- Melnick-Needles syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- otopalatodigital syndrome type 2Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- terminal osseous dysplasia-pigmentary defects syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- cardiac valvular dysplasia, X-linkedInheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- frontometaphyseal dysplasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- congenital short bowel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- otopalatodigital syndrome type 1Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- X-linked Ehlers-Danlos syndromeInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- familial thoracic aortic aneurysm and aortic dissectionInheritance: 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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000177 AC: 2AN: 112744Hom.: 0 Cov.: 25 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
112744
Hom.:
Cov.:
25
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000110 AC: 2AN: 181516 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
181516
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000365 AC: 4AN: 1097368Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 2AN XY: 363134 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1097368
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
363134
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26402
American (AMR)
AF:
AC:
0
AN:
35205
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19384
East Asian (EAS)
AF:
AC:
0
AN:
30206
South Asian (SAS)
AF:
AC:
0
AN:
54143
European-Finnish (FIN)
AF:
AC:
0
AN:
39866
Middle Eastern (MID)
AF:
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
AC:
3
AN:
841943
Other (OTH)
AF:
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
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50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome AF: 0.0000177 AC: 2AN: 112744Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 34880 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
112744
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
34880
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31020
American (AMR)
AF:
AC:
0
AN:
10764
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2656
East Asian (EAS)
AF:
AC:
0
AN:
3614
South Asian (SAS)
AF:
AC:
0
AN:
2770
European-Finnish (FIN)
AF:
AC:
0
AN:
6264
Middle Eastern (MID)
AF:
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
AC:
2
AN:
53214
Other (OTH)
AF:
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:
Hom.:
Bravo
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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