rs7063300

Variant names:

• chrX-154349351-A-G
• rs7063300
• NM_001110556.2:c.7756+11T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001110556.2(FLNA):​c.7756+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (19867 hom., 24581 hem., cov: 26)
  • Exomes 𝑓: 0.58 (129760 hom. 213779 hem.)
  • Failed GnomAD Quality Control
• Consequence: FLNA NM_001110556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 5 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 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, Illumina, Labcorp Genetics (formerly Invitae), G2P
• intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Melnick-Needles syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• otopalatodigital syndrome type 2

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• terminal osseous dysplasia-pigmentary defects syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, 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: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNA	NM_001110556.2	MANE Select	c.7756+11T>C		intron	N/A	NP_001104026.1	P21333-1
	FLNA	NM_001456.4		c.7732+11T>C		intron	N/A	NP_001447.2	P21333-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNA	ENST00000369850.10	TSL:1 MANE Select	c.7756+11T>C		intron	N/A	ENSP00000358866.3	P21333-1
	FLNA	ENST00000360319.9	TSL:1	c.7732+11T>C		intron	N/A	ENSP00000353467.4	P21333-2
	FLNA	ENST00000369856.8	TSL:1	c.7675+11T>C		intron	N/A	ENSP00000358872.4	Q60FE5

Frequencies

GnomAD3 genomes AF: 0.693 AC: 77982 AN: 112593 Hom.: 19860 Cov.: 26

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.690

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.584 AC: 638757 AN: 1092843 Hom.: 129760 Cov.: 34 AF XY: 0.595 AC XY: 213779 AN XY: 359097

African (AFR) AF: 0.946 AC: 24943 AN: 26372

American (AMR) AF: 0.842 AC: 29623 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 9598 AN: 19348

East Asian (EAS) AF: 0.999 AC: 30180 AN: 30198

South Asian (SAS) AF: 0.873 AC: 47190 AN: 54084

European-Finnish (FIN) AF: 0.600 AC: 23836 AN: 39711

Middle Eastern (MID) AF: 0.636 AC: 2599 AN: 4084

European-Non Finnish (NFE) AF: 0.527 AC: 441789 AN: 837918

Other (OTH) AF: 0.631 AC: 28999 AN: 45940

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.693 AC: 78045 AN: 112643 Hom.: 19867 Cov.: 26 AF XY: 0.706 AC XY: 24581 AN XY: 34817

African (AFR) AF: 0.938 AC: 29220 AN: 31157

American (AMR) AF: 0.771 AC: 8327 AN: 10797

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1278 AN: 2649

East Asian (EAS) AF: 0.998 AC: 3539 AN: 3546

South Asian (SAS) AF: 0.891 AC: 2493 AN: 2797

European-Finnish (FIN) AF: 0.609 AC: 3755 AN: 6168

Middle Eastern (MID) AF: 0.545 AC: 116 AN: 213

European-Non Finnish (NFE) AF: 0.527 AC: 27961 AN: 53094

Other (OTH) AF: 0.695 AC: 1080 AN: 1554

Alfa AF: 0.607 Hom.: 7030

Bravo AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7063300; hg19: chrX-153577719;