rs839232

Variant names:

• chr3-58035099-T-A
• rs839232
• NM_001457.4:c.292+26243T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001457.4(FLNB):​c.292+26243T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,054 control chromosomes in the GnomAD database, including 43,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43691 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 5 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+26243T>A		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+26243T>A		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.292+26243T>A		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.292+26243T>A		intron_variant	Intron 1 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.292+26243T>A		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113807 AN: 151936 Hom.: 43633 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 113922 AN: 152054 Hom.: 43691 Cov.: 31 AF XY: 0.754 AC XY: 56024 AN XY: 74314

African (AFR) AF: 0.880 AC: 36510 AN: 41490

American (AMR) AF: 0.754 AC: 11513 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2976 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4895 AN: 5176

South Asian (SAS) AF: 0.863 AC: 4161 AN: 4822

European-Finnish (FIN) AF: 0.638 AC: 6730 AN: 10550

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44696 AN: 67966

Other (OTH) AF: 0.766 AC: 1614 AN: 2108

Alfa AF: 0.704 Hom.: 4810

Bravo AF: 0.765

Asia WGS AF: 0.887 AC: 3085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.018
DANN	Benign	0.50
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs839232; hg19: chr3-58020826;