3-58103789-A-G

Position:

• chr3-58103789-A-G

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.1484-170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,124 control chromosomes in the GnomAD database, including 42,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.73 (42017 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.931

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=-0.86).
• BP6: Variant 3-58103789-A-G is Benign according to our data. Variant chr3-58103789-A-G is described in ClinVar as [Benign]. Clinvar id is 683080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNB	NM_001457.4	c.1484-170A>G		intron_variant		ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.1484-170A>G		intron_variant			NP_001157789.1
FLNB	NM_001164318.2	c.1484-170A>G		intron_variant			NP_001157790.1
FLNB	NM_001164319.2	c.1484-170A>G		intron_variant			NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.1484-170A>G		intron_variant		1	NM_001457.4	ENSP00000295956	A1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111550 AN: 152006 Hom.: 41944 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.734 AC: 111684 AN: 152124 Hom.: 42017 Cov.: 31 AF XY: 0.738 AC XY: 54868 AN XY: 74352

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.736

Alfa AF: 0.668 Hom.: 45471

Bravo AF: 0.754

Asia WGS AF: 0.907 AC: 3155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.86
CADD	Benign	0.81
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6445945; hg19: chr3-58089516;