chr3-58168450-G-A

Variant names:

• chr3-58168450-G-A
• rs13079906
• NM_001457.4:c.7209G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001457.4(FLNB):​c.7209G>A​(p.Ser2403Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,022 control chromosomes in the GnomAD database, including 9,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (708 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8615 hom.)
• Consequence: FLNB NM_001457.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.72
• Publications: 13 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-AS1 (HGNC:40239): (FLNB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-58168450-G-A is Benign according to our data. Variant chr3-58168450-G-A is described in ClinVar as Benign. ClinVar VariationId is 258121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.7209G>A	p.Ser2403Ser	synonymous	Exon 44 of 46	NP_001448.2
	FLNB	NM_001164317.2		c.7302G>A	p.Ser2434Ser	synonymous	Exon 45 of 47	NP_001157789.1
	FLNB	NM_001164318.2		c.7176G>A	p.Ser2392Ser	synonymous	Exon 44 of 46	NP_001157790.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000295956.9	TSL:1 MANE Select	c.7209G>A	p.Ser2403Ser	synonymous	Exon 44 of 46	ENSP00000295956.5
	FLNB	ENST00000490882.5	TSL:1	c.7302G>A	p.Ser2434Ser	synonymous	Exon 45 of 47	ENSP00000420213.1
	FLNB	ENST00000429972.6	TSL:1	c.7176G>A	p.Ser2392Ser	synonymous	Exon 44 of 46	ENSP00000415599.2

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13401 AN: 152134 Hom.: 710 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0606

GnomAD2 exomes AF: 0.0891 AC: 22390 AN: 251276 AF XY: 0.0878

Gnomad AFR exome AF: 0.0598

Gnomad AMR exome AF: 0.0893

Gnomad ASJ exome AF: 0.0660

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0918

GnomAD4 exome AF: 0.104 AC: 151642 AN: 1459770 Hom.: 8615 Cov.: 31 AF XY: 0.102 AC XY: 74094 AN XY: 726272

African (AFR) AF: 0.0558 AC: 1866 AN: 33464

American (AMR) AF: 0.0891 AC: 3984 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 1702 AN: 26128

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39696

South Asian (SAS) AF: 0.0669 AC: 5770 AN: 86214

European-Finnish (FIN) AF: 0.146 AC: 7777 AN: 53402

Middle Eastern (MID) AF: 0.0371 AC: 214 AN: 5768

European-Non Finnish (NFE) AF: 0.112 AC: 124807 AN: 1110054

Other (OTH) AF: 0.0912 AC: 5500 AN: 60330

GnomAD4 genome AF: 0.0880 AC: 13395 AN: 152252 Hom.: 708 Cov.: 33 AF XY: 0.0881 AC XY: 6554 AN XY: 74424

African (AFR) AF: 0.0616 AC: 2559 AN: 41548

American (AMR) AF: 0.0736 AC: 1127 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4826

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10586

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7431 AN: 68010

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0989 Hom.: 650

Bravo AF: 0.0828

Asia WGS AF: 0.0360 AC: 123 AN: 3478

EpiCase AF: 0.0948

EpiControl AF: 0.0925

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	FLNB-Related Spectrum Disorders (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		-1.7
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs13079906; hg19: chr3-58154177; COSMIC: COSV55869029;