rs73074072

Positions:

chr3-58105076-G-A

Variant summary

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

The NM_001457.4(FLNB):c.1611-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,978 control chromosomes in the GnomAD database, including 3,403 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 172 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3231 hom. )

Consequence

FLNB
NM_001457.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004395

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.365

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 -20 ACMG points.

BP4

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

BP6

Variant 3-58105076-G-A is Benign according to our data. Variant chr3-58105076-G-A is described in ClinVar as [Benign]. Clinvar id is 258099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58105076-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FLNB	NM_001457.4 linkuse as main transcript	c.1611-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000295956.9
FLNB	NM_001164317.2 linkuse as main transcript	c.1611-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
FLNB	NM_001164318.2 linkuse as main transcript	c.1611-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
FLNB	NM_001164319.2 linkuse as main transcript	c.1611-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9 linkuse as main transcript	c.1611-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001457.4	A1	O75369-1

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6242

AN:

152184

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0652

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0445

AC:

11200

AN:

251480

Hom.:

366

AF XY:

0.0455

AC XY:

6181

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0348

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0638

Gnomad OTH exome

AF:

0.0567

GnomAD4 exome

AF:

0.0619

AC:

90538

AN:

1461676

Hom.:

3231

Cov.:

AF XY:

0.0610

AC XY:

44348

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0241

Gnomad4 ASJ exome

AF:

0.0686

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0352

Gnomad4 FIN exome

AF:

0.0435

Gnomad4 NFE exome

AF:

0.0704

Gnomad4 OTH exome

AF:

0.0556

GnomAD4 genome

AF:

0.0410

AC:

6242

AN:

152302

Hom.:

172

Cov.:

AF XY:

0.0394

AC XY:

2932

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0229

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0652

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0606

Hom.:

157

Bravo

AF:

0.0388

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0608

EpiControl

AF:

0.0650

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	Jun 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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 07, 2023	- -

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. -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.0

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.0

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