X-154348764-C-CCA

Position:

• chrX-154348764-C-CCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001110556.2(FLNA):​c.*84_*85insTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 984,398 control chromosomes in the GnomAD database, including 6,530 homozygotes. There are 36,733 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1311 hom., 5193 hem., cov: 24)
  • Exomes 𝑓: 0.12 (5219 hom. 31540 hem.)
• Consequence: FLNA NM_001110556.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.718

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 -10 ACMG points.

• BP6: Variant X-154348764-C-CCA is Benign according to our data. Variant chrX-154348764-C-CCA is described in ClinVar as [Benign]. Clinvar id is 1246232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNA	NM_001110556.2	c.*84_*85insTG		3_prime_UTR_variant	48/48	ENST00000369850.10
FLNA	NM_001456.4	c.*84_*85insTG		3_prime_UTR_variant	47/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNA	ENST00000369850.10	c.*84_*85insTG		3_prime_UTR_variant	48/48	1	NM_001110556.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 17736 AN: 111316 Hom.: 1306 Cov.: 24 AF XY: 0.154 AC XY: 5161 AN XY: 33598

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.00292

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0537

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.124 AC: 108058 AN: 873036 Hom.: 5219 Cov.: 14 AF XY: 0.130 AC XY: 31540 AN XY: 242538

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0591

Gnomad4 EAS exome AF: 0.0706

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.160 AC: 17777 AN: 111362 Hom.: 1311 Cov.: 24 AF XY: 0.154 AC XY: 5193 AN XY: 33654

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0537

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0329 Hom.: 146

Asia WGS AF: 0.145 AC: 363 AN: 2521

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201431046; hg19: chrX-153577132; COSMIC: COSV61049289; COSMIC: COSV61049289;