rs2177153

chr3-58106619-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001457.4(FLNB):c.1748-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,502,124 control chromosomes in the GnomAD database, including 68,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6787 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61398 hom.)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0340

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-58106619-A-G is Benign according to our data. Variant chr3-58106619-A-G is described in ClinVar as [Benign]. Clinvar id is 675060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.1748-61A>G		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.1748-61A>G		intron_variant
FLNB	NM_001164318.2	c.1748-61A>G		intron_variant
FLNB	NM_001164319.2	c.1748-61A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.1748-61A>G		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43843 AN: 151836 Hom.: 6766 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.293 AC: 395180 AN: 1350170 Hom.: 61398 AF XY: 0.292 AC XY: 197661 AN XY: 677960

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.289 AC: 43902 AN: 151954 Hom.: 6787 Cov.: 31 AF XY: 0.284 AC XY: 21085 AN XY: 74260

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.302

Alfa AF: 0.308 Hom.: 15738

Bravo AF: 0.289

Asia WGS AF: 0.115 AC: 404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.34

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: rs2177153; hg19: chr3-58092346;