rs1718454

Variant names:

• chr3-58065221-A-G
• rs1718454
• NM_001457.4:c.293-11825A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-58065221-A-G
• chr3-58065221-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001457.4(FLNB):​c.293-11825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,094 control chromosomes in the GnomAD database, including 26,962 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 0.56 (26962 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.293-11825A>G		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.293-11825A>G		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.293-11825A>G		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.293-11825A>G		intron_variant	Intron 1 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.293-11825A>G		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84505 AN: 151976 Hom.: 26887 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.557 AC: 84643 AN: 152094 Hom.: 26962 Cov.: 32 AF XY: 0.552 AC XY: 41004 AN XY: 74328

African (AFR) AF: 0.878 AC: 36464 AN: 41540

American (AMR) AF: 0.505 AC: 7720 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1958 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3266 AN: 5154

South Asian (SAS) AF: 0.383 AC: 1838 AN: 4804

European-Finnish (FIN) AF: 0.355 AC: 3754 AN: 10574

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28062 AN: 67950

Other (OTH) AF: 0.547 AC: 1157 AN: 2116

Alfa AF: 0.453 Hom.: 12793

Bravo AF: 0.586

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.6
DANN	Benign	0.42
PhyloP100		0.11
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: rs1718454; hg19: chr3-58050948;