rs4681784

Variant names:

• chr3-58085917-C-A
• rs4681784
• NM_001457.4:c.787+4141C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58085917-C-A
• chr3-58085917-C-G
• chr3-58085917-C-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.787+4141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,004 control chromosomes in the GnomAD database, including 18,890 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 0.47 (18890 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.787+4141C>A		intron_variant	Intron 4 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.787+4141C>A		intron_variant	Intron 4 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.787+4141C>A		intron_variant	Intron 4 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.787+4141C>A		intron_variant	Intron 4 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.787+4141C>A		intron_variant	Intron 4 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70955 AN: 151886 Hom.: 18850 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.467 AC: 71052 AN: 152004 Hom.: 18890 Cov.: 31 AF XY: 0.476 AC XY: 35360 AN XY: 74304

African (AFR) AF: 0.624 AC: 25880 AN: 41464

American (AMR) AF: 0.551 AC: 8419 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5053 AN: 5178

South Asian (SAS) AF: 0.599 AC: 2889 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3706 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22604 AN: 67924

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.379 Hom.: 47285

Bravo AF: 0.491

Asia WGS AF: 0.793 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4681784; hg19: chr3-58071644;