rs1718481

Variant names:

• chr3-58040176-C-T
• rs1718481
• NM_001457.4:c.292+31320C>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.292+31320C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,002 control chromosomes in the GnomAD database, including 21,762 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 0.52 (21762 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+31320C>T		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+31320C>T		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.292+31320C>T		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.292+31320C>T		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.292+31320C>T		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78782 AN: 151884 Hom.: 21732 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.519 AC: 78869 AN: 152002 Hom.: 21762 Cov.: 31 AF XY: 0.517 AC XY: 38412 AN XY: 74294

African (AFR) AF: 0.715 AC: 29655 AN: 41468

American (AMR) AF: 0.479 AC: 7313 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2098 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2560 AN: 5164

South Asian (SAS) AF: 0.444 AC: 2136 AN: 4812

European-Finnish (FIN) AF: 0.427 AC: 4504 AN: 10554

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29095 AN: 67950

Other (OTH) AF: 0.515 AC: 1085 AN: 2108

Alfa AF: 0.467 Hom.: 28929

Bravo AF: 0.536

Asia WGS AF: 0.461 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.085
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: rs1718481; hg19: chr3-58025903;