rs2033739

Variant names:

• chr3-58078092-G-A
• rs2033739
• NM_001457.4:c.542-625G>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.542-625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,180 control chromosomes in the GnomAD database, including 5,976 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 0.26 (5976 hom., cov: 33)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.542-625G>A		intron_variant	Intron 2 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.542-625G>A		intron_variant	Intron 2 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.542-625G>A		intron_variant	Intron 2 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.542-625G>A		intron_variant	Intron 2 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.542-625G>A		intron_variant	Intron 2 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38793 AN: 152062 Hom.: 5969 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.255 AC: 38808 AN: 152180 Hom.: 5976 Cov.: 33 AF XY: 0.251 AC XY: 18678 AN XY: 74416

African (AFR) AF: 0.128 AC: 5310 AN: 41542

American (AMR) AF: 0.214 AC: 3264 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1468 AN: 3466

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5192

South Asian (SAS) AF: 0.286 AC: 1381 AN: 4826

European-Finnish (FIN) AF: 0.272 AC: 2878 AN: 10572

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23429 AN: 67986

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.322 Hom.: 4314

Bravo AF: 0.241

Asia WGS AF: 0.137 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.19
PhyloP100		-1.4
PromoterAI		-0.019	Neutral
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: rs2033739; hg19: chr3-58063819;