3-58096161-T-C

Position:

chr3-58096161-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001457.4(FLNB):c.927T>C(p.Ser309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,612,054 control chromosomes in the GnomAD database, including 135,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16734 hom., cov: 32)

Exomes 𝑓: 0.38 ( 118969 hom. )

Consequence

FLNB
NM_001457.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.88

Variant links:

Genes affected

FLNB (HGNC:3755): (filamin B) This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

FLNB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-58096161-T-C is Benign according to our data. Variant chr3-58096161-T-C is described in ClinVar as [Benign]. Clinvar id is 258123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58096161-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FLNB	NM_001457.4 linkuse as main transcript	c.927T>C	p.Ser309=	synonymous_variant	6/46	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2 linkuse as main transcript	c.927T>C	p.Ser309=	synonymous_variant	6/47		NP_001157789.1
FLNB	NM_001164318.2 linkuse as main transcript	c.927T>C	p.Ser309=	synonymous_variant	6/46		NP_001157790.1
FLNB	NM_001164319.2 linkuse as main transcript	c.927T>C	p.Ser309=	synonymous_variant	6/45		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9 linkuse as main transcript	c.927T>C	p.Ser309=	synonymous_variant	6/46	1	NM_001457.4	ENSP00000295956	A1	O75369-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67188

AN:

151902

Hom.:

16709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.975

Gnomad SAS

AF:

0.630

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.469

AC:

117670

AN:

250958

Hom.:

32846

AF XY:

0.460

AC XY:

62372

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.975

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.379

AC:

553545

AN:

1460034

Hom.:

118969

Cov.:

AF XY:

0.383

AC XY:

278118

AN XY:

726420

show subpopulations

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.653

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.572

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.442

AC:

67260

AN:

152020

Hom.:

16734

Cov.:

AF XY:

0.451

AC XY:

33514

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.975

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.350

Hom.:

3653

Bravo

AF:

0.461

Asia WGS

AF:

0.791

AC:

2750

AN:

3478

EpiCase

AF:

0.326

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FLNB-Related Spectrum Disorders

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.91

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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