Variant chrX-154348765-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001110556.2(FLNA):c.*84A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 982,339 control chromosomes in the GnomAD database, including 6,645 homozygotes. There are 36,799 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1311 hom., 5235 hem., cov: 24)

Exomes 𝑓: 0.13 ( 5334 hom. 31564 hem. )

Consequence

FLNA
NM_001110556.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.718

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-154348765-T-G is Benign according to our data. Variant chrX-154348765-T-G is described in ClinVar as [Benign]. Clinvar id is 1258029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNA	NM_001110556.2 linkuse as main transcript	c.*84A>C		3_prime_UTR_variant	48/48	ENST00000369850.10	NP_001104026.1
FLNA	NM_001456.4 linkuse as main transcript	c.*84A>C		3_prime_UTR_variant	47/47		NP_001447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850.10 linkuse as main transcript	c.*84A>C		3_prime_UTR_variant	48/48	1	NM_001110556.2	ENSP00000358866		P21333-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

17778

AN:

110890

Hom.:

1306

Cov.:

AF XY:

0.157

AC XY:

5203

AN XY:

33242

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.00295

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.0540

Gnomad EAS

AF:

0.0573

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0515

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.126

AC:

109371

AN:

871402

Hom.:

5334

Cov.:

AF XY:

0.131

AC XY:

31564

AN XY:

240428

show subpopulations

Gnomad4 AFR exome

AF:

0.288

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.0596

Gnomad4 EAS exome

AF:

0.0706

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.161

AC:

17819

AN:

110937

Hom.:

1311

Cov.:

AF XY:

0.157

AC XY:

5235

AN XY:

33299

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.0540

Gnomad4 EAS

AF:

0.0563

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.0396

Hom.:

146

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

DANN

Benign

0.48

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