3-58120049-C-T

Position:

• chr3-58120049-C-T

Variant summary

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

The NM_001457.4(FLNB):​c.2863+1060C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,154 control chromosomes in the GnomAD database, including 4,087 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 0.20 (4087 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNB	NM_001457.4	c.2863+1060C>T		intron_variant		ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.2863+1060C>T		intron_variant			NP_001157789.1
FLNB	NM_001164318.2	c.2863+1060C>T		intron_variant			NP_001157790.1
FLNB	NM_001164319.2	c.2863+1060C>T		intron_variant			NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.2863+1060C>T		intron_variant		1	NM_001457.4	ENSP00000295956	A1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31133 AN: 152036 Hom.: 4079 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.205 AC: 31148 AN: 152154 Hom.: 4087 Cov.: 32 AF XY: 0.201 AC XY: 14977 AN XY: 74384

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.231

Alfa AF: 0.146 Hom.: 269

Bravo AF: 0.193

Asia WGS AF: 0.0900 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.45

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: rs13077017; hg19: chr3-58105776;