rs720163

chr1-240132575-A-G

Variant summary

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

The NM_020066.5(FMN2):c.1782+9230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,000 control chromosomes in the GnomAD database, including 6,988 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 0.28 (6988 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5	c.1782+9230A>G		intron_variant		ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.1782+9230A>G		intron_variant		5	NM_020066.5	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42967 AN: 151882 Hom.: 6988 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.283 AC: 42983 AN: 152000 Hom.: 6988 Cov.: 32 AF XY: 0.281 AC XY: 20875 AN XY: 74298

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.316

Alfa AF: 0.314 Hom.: 1281

Bravo AF: 0.273

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	6.2
Dann	Benign	0.64

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: rs720163; hg19: chr1-240295875;