rs2001972

Variant names:

• chr3-58137522-C-A
• rs2001972
• NM_001457.4:c.4862-760C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58137522-C-A
• chr3-58137522-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.4862-760C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,148 control chromosomes in the GnomAD database, including 8,266 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 0.32 (8266 hom., cov: 33)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.4862-760C>A		intron_variant	Intron 28 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.4955-760C>A		intron_variant	Intron 29 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.4862-760C>A		intron_variant	Intron 28 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.4862-760C>A		intron_variant	Intron 28 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.4862-760C>A		intron_variant	Intron 28 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48328 AN: 152030 Hom.: 8252 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.318 AC: 48377 AN: 152148 Hom.: 8266 Cov.: 33 AF XY: 0.313 AC XY: 23319 AN XY: 74404

African (AFR) AF: 0.283 AC: 11749 AN: 41488

American (AMR) AF: 0.257 AC: 3938 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5192

South Asian (SAS) AF: 0.223 AC: 1078 AN: 4824

European-Finnish (FIN) AF: 0.322 AC: 3410 AN: 10584

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25692 AN: 67976

Other (OTH) AF: 0.314 AC: 665 AN: 2116

Alfa AF: 0.360 Hom.: 20331

Bravo AF: 0.313

Asia WGS AF: 0.133 AC: 463 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	0.070
DANN	Benign	0.57
PhyloP100		-1.8
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: rs2001972; hg19: chr3-58123249;