rs2001972

Positions:

• chr3-58137522-C-A
• chr3-58137522-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295956.9(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 ENST00000295956.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FLNB	NM_001457.4	c.4862-760C>A		intron_variant		ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.4955-760C>A		intron_variant			NP_001157789.1
FLNB	NM_001164318.2	c.4862-760C>A		intron_variant			NP_001157790.1
FLNB	NM_001164319.2	c.4862-760C>A		intron_variant			NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.4862-760C>A		intron_variant		1	NM_001457.4	ENSP00000295956	A1

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

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.314

Alfa AF: 0.361 Hom.: 14839

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2001972; hg19: chr3-58123249;