rs12634123

chr3-58159536-G-Achr3-58159536-G-Cchr3-58159536-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001457.4(FLNB):c.6889-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,612,544 control chromosomes in the GnomAD database, including 335,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31631 hom., cov: 32)
  • Exomes 𝑓: 0.64 (303619 hom.)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.113

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-58159536-G-A is Benign according to our data. Variant chr3-58159536-G-A is described in ClinVar as [Benign]. Clinvar id is 258119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58159536-G-A is described in Lovd as [Likely_benign]. Variant chr3-58159536-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.6889-18G>A		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.6982-18G>A		intron_variant
FLNB	NM_001164318.2	c.6856-18G>A		intron_variant
FLNB	NM_001164319.2	c.6817-18G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.6889-18G>A		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97172 AN: 151944 Hom.: 31602 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.641

GnomAD3 exomes AF: 0.672 AC: 168874 AN: 251232 Hom.: 58543 AF XY: 0.669 AC XY: 90888 AN XY: 135836

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.745

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.612

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.640 AC: 935294 AN: 1460482 Hom.: 303619 Cov.: 39 AF XY: 0.642 AC XY: 466791 AN XY: 726608

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.640 AC: 97251 AN: 152062 Hom.: 31631 Cov.: 32 AF XY: 0.644 AC XY: 47819 AN XY: 74308

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.646

Alfa AF: 0.636 Hom.: 7869

Bravo AF: 0.650

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	9.9
Dann	Benign	0.85

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: rs12634123; hg19: chr3-58145263;