rs3772993

Variant names:

• chr3-58129157-C-T
• rs3772993
• NM_001457.4:c.4223-1584C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001457.4(FLNB):​c.4223-1584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,948 control chromosomes in the GnomAD database, including 13,617 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 0.39 (13617 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• 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: 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 = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.4223-1584C>T		intron_variant	Intron 24 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.4223-1584C>T		intron_variant	Intron 24 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.4223-1584C>T		intron_variant	Intron 24 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.4223-1584C>T		intron_variant	Intron 24 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.4223-1584C>T		intron_variant	Intron 24 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58627 AN: 151828 Hom.: 13598 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.386 AC: 58688 AN: 151948 Hom.: 13617 Cov.: 32 AF XY: 0.394 AC XY: 29292 AN XY: 74282

African (AFR) AF: 0.552 AC: 22847 AN: 41400

American (AMR) AF: 0.451 AC: 6890 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3464

East Asian (EAS) AF: 0.913 AC: 4714 AN: 5162

South Asian (SAS) AF: 0.534 AC: 2575 AN: 4818

European-Finnish (FIN) AF: 0.260 AC: 2751 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16903 AN: 67960

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.339 Hom.: 1739

Bravo AF: 0.408

Asia WGS AF: 0.725 AC: 2521 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	2.4
DANN	Benign	0.67
PhyloP100		-0.24
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: rs3772993; hg19: chr3-58114884;