NM_001457.4:c.293-5089G>T

Variant names:

• chr3-58071957-G-T
• rs9822918
• NM_001457.4:c.293-5089G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001457.4(FLNB):​c.293-5089G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,028 control chromosomes in the GnomAD database, including 23,026 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 0.53 (23026 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.293-5089G>T		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.293-5089G>T		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.293-5089G>T		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.293-5089G>T		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.293-5089G>T		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81161 AN: 151908 Hom.: 22981 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.534 AC: 81257 AN: 152028 Hom.: 23026 Cov.: 32 AF XY: 0.530 AC XY: 39408 AN XY: 74330

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.528

Alfa AF: 0.468 Hom.: 33670

Bravo AF: 0.547

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.73

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: rs9822918; hg19: chr3-58057684;