3-58020686-A-G

Variant names:

• chr3-58020686-A-G
• rs1718460
• NM_001457.4:c.292+11830A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001457.4(FLNB):​c.292+11830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 149,472 control chromosomes in the GnomAD database, including 45,335 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 0.77 (45335 hom., cov: 24)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 3 publications found

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]

FLNB Gene-Disease associations (from GenCC):

• atelosteogenesis type I

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• atelosteogenesis type III

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• Larsen syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• spondylocarpotarsal synostosis syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• Boomerang dysplasia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001457.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.292+11830A>G		intron	N/A	NP_001448.2
	FLNB	NM_001164317.2		c.292+11830A>G		intron	N/A	NP_001157789.1
	FLNB	NM_001164318.2		c.292+11830A>G		intron	N/A	NP_001157790.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000295956.9	TSL:1 MANE Select	c.292+11830A>G		intron	N/A	ENSP00000295956.5
	FLNB	ENST00000490882.5	TSL:1	c.292+11830A>G		intron	N/A	ENSP00000420213.1
	FLNB	ENST00000429972.6	TSL:1	c.292+11830A>G		intron	N/A	ENSP00000415599.2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 114979 AN: 149364 Hom.: 45282 Cov.: 24

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.770 AC: 115084 AN: 149472 Hom.: 45335 Cov.: 24 AF XY: 0.775 AC XY: 56383 AN XY: 72722

African (AFR) AF: 0.913 AC: 36903 AN: 40414

American (AMR) AF: 0.769 AC: 11561 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3016 AN: 3468

East Asian (EAS) AF: 0.953 AC: 4818 AN: 5054

South Asian (SAS) AF: 0.859 AC: 4020 AN: 4680

European-Finnish (FIN) AF: 0.678 AC: 6748 AN: 9948

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.673 AC: 45531 AN: 67624

Other (OTH) AF: 0.783 AC: 1618 AN: 2066

Alfa AF: 0.719 Hom.: 5351

Bravo AF: 0.785

Asia WGS AF: 0.888 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.83
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1718460; hg19: chr3-58006413;