1-240392735-T-C

Position:

• chr1-240392735-T-C

Variant summary

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

The NM_020066.5(FMN2):​c.4910+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,030 control chromosomes in the GnomAD database, including 24,282 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 0.55 (24282 hom., cov: 33)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN2	NM_020066.5	c.4910+173T>C		intron_variant		ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.4910+173T>C		intron_variant		5	NM_020066.5	ENSP00000318884.9

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83132 AN: 151910 Hom.: 24225 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.548 AC: 83253 AN: 152030 Hom.: 24282 Cov.: 33 AF XY: 0.542 AC XY: 40272 AN XY: 74330

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.535

Alfa AF: 0.495 Hom.: 2358

Bravo AF: 0.574

Asia WGS AF: 0.611 AC: 2118 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.19
DANN	Benign	0.60

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: rs9730073; hg19: chr1-240556035;