NM_001457.4:c.292+14676G>C

Variant names:

• chr3-58023532-G-C
• rs1658342
• NM_001457.4:c.292+14676G>C

Variant summary

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

The NM_001457.4(FLNB):​c.292+14676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,192 control chromosomes in the GnomAD database, including 44,215 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 0.76 (44215 hom., cov: 33)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+14676G>C		intron_variant	Intron 1 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+14676G>C		intron_variant	Intron 1 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.292+14676G>C		intron_variant	Intron 1 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.292+14676G>C		intron_variant	Intron 1 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.292+14676G>C		intron_variant	Intron 1 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114853 AN: 152074 Hom.: 44172 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.755 AC: 114949 AN: 152192 Hom.: 44215 Cov.: 33 AF XY: 0.760 AC XY: 56572 AN XY: 74412

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.777

Alfa AF: 0.581 Hom.: 1522

Bravo AF: 0.767

Asia WGS AF: 0.887 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.0
DANN	Benign	0.71

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: rs1658342; hg19: chr3-58009259;