rs9283429

Positions:

• chr1-240398647-C-T

Variant summary

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

The NM_020066.5(FMN2):​c.4910+6085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,122 control chromosomes in the GnomAD database, including 610 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 0.085 (610 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

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 (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5	c.4910+6085C>T		intron_variant		ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.4910+6085C>T		intron_variant		5	NM_020066.5	P1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12874 AN: 152004 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0847 AC: 12883 AN: 152122 Hom.: 610 Cov.: 32 AF XY: 0.0816 AC XY: 6067 AN XY: 74360

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.0619

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0407

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0840 Hom.: 360

Bravo AF: 0.0891

Asia WGS AF: 0.0770 AC: 269 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	4.9
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: rs9283429; hg19: chr1-240561947;