3-58041470-A-G

Variant names:

• chr3-58041470-A-G
• rs1623879
• NM_001457.4:c.292+32614A>G

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+32614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,784 control chromosomes in the GnomAD database, including 4,850 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 0.21 (4850 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+32614A>G		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+32614A>G		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.292+32614A>G		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.292+32614A>G		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+32614A>G		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31702 AN: 151666 Hom.: 4836 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.209 AC: 31762 AN: 151784 Hom.: 4850 Cov.: 31 AF XY: 0.212 AC XY: 15726 AN XY: 74190

African (AFR) AF: 0.393 AC: 16235 AN: 41286

American (AMR) AF: 0.244 AC: 3724 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2487 AN: 5114

South Asian (SAS) AF: 0.141 AC: 678 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1224 AN: 10572

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0952 AC: 6470 AN: 67958

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.160 Hom.: 4643

Bravo AF: 0.234

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		-0.041
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: rs1623879; hg19: chr3-58027197;