rs8640

Variant names:

• chr3-58168600-C-T
• rs8640
• NM_001457.4:c.7359C>T

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.7359C>T​(p.Ser2453Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,613,232 control chromosomes in the GnomAD database, including 95,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12694 hom., cov: 33)
  • Exomes 𝑓: 0.31 (82433 hom.)
• Consequence: FLNB NM_001457.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.06
• Publications: 31 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=-0.53).
• BP6: Variant 3-58168600-C-T is Benign according to our data. Variant chr3-58168600-C-T is described in ClinVar as Benign. ClinVar VariationId is 258122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 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.7359C>T	p.Ser2453Ser	synonymous	Exon 44 of 46	NP_001448.2
	FLNB	NM_001164317.2		c.7452C>T	p.Ser2484Ser	synonymous	Exon 45 of 47	NP_001157789.1
	FLNB	NM_001164318.2		c.7326C>T	p.Ser2442Ser	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.7359C>T	p.Ser2453Ser	synonymous	Exon 44 of 46	ENSP00000295956.5
	FLNB	ENST00000490882.5	TSL:1	c.7452C>T	p.Ser2484Ser	synonymous	Exon 45 of 47	ENSP00000420213.1
	FLNB	ENST00000429972.6	TSL:1	c.7326C>T	p.Ser2442Ser	synonymous	Exon 44 of 46	ENSP00000415599.2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57258 AN: 151918 Hom.: 12678 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.387 AC: 97186 AN: 251398 AF XY: 0.378

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.918

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.307 AC: 448303 AN: 1461196 Hom.: 82433 Cov.: 36 AF XY: 0.309 AC XY: 224898 AN XY: 726922

African (AFR) AF: 0.522 AC: 17472 AN: 33466

American (AMR) AF: 0.513 AC: 22944 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5916 AN: 26136

East Asian (EAS) AF: 0.928 AC: 36853 AN: 39698

South Asian (SAS) AF: 0.476 AC: 41064 AN: 86228

European-Finnish (FIN) AF: 0.252 AC: 13454 AN: 53420

Middle Eastern (MID) AF: 0.279 AC: 1606 AN: 5746

European-Non Finnish (NFE) AF: 0.260 AC: 288580 AN: 1111410

Other (OTH) AF: 0.338 AC: 20414 AN: 60376

GnomAD4 genome AF: 0.377 AC: 57319 AN: 152036 Hom.: 12694 Cov.: 33 AF XY: 0.385 AC XY: 28593 AN XY: 74314

African (AFR) AF: 0.510 AC: 21118 AN: 41438

American (AMR) AF: 0.441 AC: 6736 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.913 AC: 4728 AN: 5180

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2721 AN: 10582

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17448 AN: 67962

Other (OTH) AF: 0.354 AC: 748 AN: 2112

Alfa AF: 0.302 Hom.: 4289

Bravo AF: 0.396

Asia WGS AF: 0.719 AC: 2499 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.259

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	-0.53
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		-1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs8640; hg19: chr3-58154327; COSMIC: COSV55869043; COSMIC: COSV55869043;