3-58023532-G-C

Variant names:

• chr3-58023532-G-C
• rs1658342
• NM_001457.4:c.292+14676G>C

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+14676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,192 control chromosomes in the GnomAD database, including 44,215 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 0.76 (44215 hom., cov: 33)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 6 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• atelosteogenesis type III

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

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.292+14676G>C		intron	N/A	NP_001448.2	O75369-1
	FLNB	NM_001164317.2		c.292+14676G>C		intron	N/A	NP_001157789.1	O75369-8
	FLNB	NM_001164318.2		c.292+14676G>C		intron	N/A	NP_001157790.1	O75369-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000295956.9	TSL:1 MANE Select	c.292+14676G>C		intron	N/A	ENSP00000295956.5	O75369-1
	FLNB	ENST00000490882.5	TSL:1	c.292+14676G>C		intron	N/A	ENSP00000420213.1	O75369-8
	FLNB	ENST00000429972.6	TSL:1	c.292+14676G>C		intron	N/A	ENSP00000415599.2	O75369-9

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114853 AN: 152074 Hom.: 44172 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.755 AC: 114949 AN: 152192 Hom.: 44215 Cov.: 33 AF XY: 0.760 AC XY: 56572 AN XY: 74412

African (AFR) AF: 0.861 AC: 35791 AN: 41546

American (AMR) AF: 0.764 AC: 11682 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3472

East Asian (EAS) AF: 0.942 AC: 4886 AN: 5188

South Asian (SAS) AF: 0.862 AC: 4159 AN: 4826

European-Finnish (FIN) AF: 0.680 AC: 7177 AN: 10560

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45716 AN: 67992

Other (OTH) AF: 0.777 AC: 1642 AN: 2112

Alfa AF: 0.581 Hom.: 1522

Bravo AF: 0.767

Asia WGS AF: 0.887 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.0
DANN	Benign	0.71
PhyloP100		0.14
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1658342;

hg19: chr3-58009259;