rs1718456

chr3-58026621-G-Achr3-58026621-G-C

Variant summary

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

The NM_001457.4(FLNB):c.292+17765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,028 control chromosomes in the GnomAD database, including 2,905 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 0.14 (2905 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.292+17765G>A		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.292+17765G>A		intron_variant
FLNB	NM_001164318.2	c.292+17765G>A		intron_variant
FLNB	NM_001164319.2	c.292+17765G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.292+17765G>A		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21290 AN: 151910 Hom.: 2900 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.140 AC: 21331 AN: 152028 Hom.: 2905 Cov.: 31 AF XY: 0.143 AC XY: 10646 AN XY: 74342

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.0907

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0609 Hom.: 724

Bravo AF: 0.165

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.38
Dann	Benign	0.67

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: rs1718456; hg19: chr3-58012348;