rs2033739

chr3-58078092-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FLNB	NM_001457.4	c.542-625G>A		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.542-625G>A		intron_variant
FLNB	NM_001164318.2	c.542-625G>A		intron_variant
FLNB	NM_001164319.2	c.542-625G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.542-625G>A		intron_variant		1	NM_001457.4	A1

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.270

Alfa AF: 0.323 Hom.: 3870

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2033739; hg19: chr3-58063819;