rs3732632

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001457.4(FLNB):c.4062-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FLNB
NM_001457.4 splice_region, intron

Scores

Splicing: ADA: 0.00007809

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.386

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

atelosteogenesis type I
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
atelosteogenesis type III
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
Larsen syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
spondylocarpotarsal synostosis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
Boomerang dysplasia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

FLNB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-58126597-T-C is Benign according to our data. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58126597-T-C is described in CliVar as Likely_benign. Clinvar id is 1634848.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4 link	c.4062-5T>C	splice_region_variant, intron_variant	Intron 23 of 45	ENST00000295956.9	NP_001448.2	O75369-1
FLNB	NM_001164317.2 link	c.4062-5T>C	splice_region_variant, intron_variant	Intron 23 of 46		NP_001157789.1	O75369-8
FLNB	NM_001164318.2 link	c.4062-5T>C	splice_region_variant, intron_variant	Intron 23 of 45		NP_001157790.1	O75369-9
FLNB	NM_001164319.2 link	c.4062-5T>C	splice_region_variant, intron_variant	Intron 23 of 44		NP_001157791.1	O75369-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9 link	c.4062-5T>C		splice_region_variant, intron_variant	Intron 23 of 45	1	NM_001457.4	ENSP00000295956.5		O75369-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251418

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461612

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111832

Other (OTH)

AF:

0.0000331

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000399

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 22, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

(source)

DANN

Benign

0.61

PhyloP100

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over