3-58026621-G-A

Variant names:

• chr3-58026621-G-A
• rs1718456
• NM_001457.4:c.292+17765G>A

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+17765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,028 control chromosomes in the GnomAD database, including 2,905 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 0.14 (2905 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+17765G>A		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+17765G>A		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.292+17765G>A		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.292+17765G>A		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+17765G>A		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21290 AN: 151910 Hom.: 2900 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.140 AC: 21331 AN: 152028 Hom.: 2905 Cov.: 31 AF XY: 0.143 AC XY: 10646 AN XY: 74342

African (AFR) AF: 0.311 AC: 12862 AN: 41394

American (AMR) AF: 0.181 AC: 2771 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5162

South Asian (SAS) AF: 0.0907 AC: 437 AN: 4816

European-Finnish (FIN) AF: 0.0436 AC: 462 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0289 AC: 1964 AN: 67992

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.0745 Hom.: 1313

Bravo AF: 0.165

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.67
PhyloP100		-1.6
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: rs1718456; hg19: chr3-58012348;