NM_001457.4:c.1484-170A>G

Variant names:

• chr3-58103789-A-G
• rs6445945
• NM_001457.4:c.1484-170A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001457.4(FLNB):​c.1484-170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,124 control chromosomes in the GnomAD database, including 42,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.73 (42017 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.931
• Publications: 9 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), Orphanet, G2P
• atelosteogenesis type III

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

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-58103789-A-G is Benign according to our data. Variant chr3-58103789-A-G is described in ClinVar as Benign. ClinVar VariationId is 683080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1484-170A>G		intron	N/A	NP_001448.2	O75369-1
	FLNB	NM_001164317.2		c.1484-170A>G		intron	N/A	NP_001157789.1	O75369-8
	FLNB	NM_001164318.2		c.1484-170A>G		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.1484-170A>G		intron	N/A	ENSP00000295956.5	O75369-1
	FLNB	ENST00000490882.5	TSL:1	c.1484-170A>G		intron	N/A	ENSP00000420213.1	O75369-8
	FLNB	ENST00000429972.6	TSL:1	c.1484-170A>G		intron	N/A	ENSP00000415599.2	O75369-9

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111550 AN: 152006 Hom.: 41944 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.734 AC: 111684 AN: 152124 Hom.: 42017 Cov.: 31 AF XY: 0.738 AC XY: 54868 AN XY: 74352

African (AFR) AF: 0.875 AC: 36315 AN: 41520

American (AMR) AF: 0.757 AC: 11568 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2348 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5182

South Asian (SAS) AF: 0.806 AC: 3879 AN: 4814

European-Finnish (FIN) AF: 0.599 AC: 6323 AN: 10552

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43724 AN: 67972

Other (OTH) AF: 0.736 AC: 1557 AN: 2116

Alfa AF: 0.677 Hom.: 59444

Bravo AF: 0.754

Asia WGS AF: 0.907 AC: 3155 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.75
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6445945; hg19: chr3-58089516;