rs7063300

chrX-154349351-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 19860 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNA	NM_001110556.2	c.7756+11T>C		intron_variant		ENST00000369850.10
FLNA	NM_001456.4	c.7732+11T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNA	ENST00000369850.10	c.7756+11T>C		intron_variant		1	NM_001110556.2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 77982 AN: 112593 Hom.: 19860 Cov.: 26 AF XY: 0.706 AC XY: 24523 AN XY: 34757

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

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.873

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.631

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

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.695

Alfa AF: 0.607 Hom.: 7030

Bravo AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7063300; hg19: chrX-153577719;