Variant X-154348732-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001110556.2(FLNA):c.*117C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 653,514 control chromosomes in the GnomAD database, including 120 homozygotes. There are 1,004 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 80 hom., 663 hem., cov: 24)

Exomes 𝑓: 0.0027 ( 40 hom. 341 hem. )

Consequence

FLNA
NM_001110556.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.360

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-154348732-G-A is Benign according to our data. Variant chrX-154348732-G-A is described in ClinVar as [Benign]. Clinvar id is 1242239.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNA	NM_001110556.2 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	48/48	ENST00000369850.10
FLNA	NM_001456.4 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	47/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNA	ENST00000369850.10 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	48/48	1	NM_001110556.2		P21333-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

2455

AN:

110218

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

660

AN XY:

32458

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00677

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000247

Gnomad OTH

AF:

0.0259

GnomAD4 exome

AF:

0.00268

AC:

1457

AN:

543251

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

341

AN XY:

149643

show subpopulations

Gnomad4 AFR exome

AF:

0.0777

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000884

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.00582

GnomAD4 genome

AF:

0.0223

AC:

2461

AN:

110263

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

663

AN XY:

32513

show subpopulations

Gnomad4 AFR

AF:

0.0782

Gnomad4 AMR

AF:

0.00676

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000247

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.5

DANN

Benign

0.75

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over