rs9287234

Positions:

• chr1-240403073-G-A
• chr1-240403073-G-C
• chr1-240403073-G-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+10511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,182 control chromosomes in the GnomAD database, including 52,207 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 0.83 (52207 hom., cov: 33)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN2	NM_020066.5	c.4910+10511G>A		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+10511G>A		intron_variant		5	NM_020066.5	ENSP00000318884	P1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125858 AN: 152060 Hom.: 52155 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.828 AC: 125974 AN: 152182 Hom.: 52207 Cov.: 33 AF XY: 0.824 AC XY: 61269 AN XY: 74378

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.874

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.846

Alfa AF: 0.833 Hom.: 6561

Bravo AF: 0.829

Asia WGS AF: 0.850 AC: 2950 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.26

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: rs9287234; hg19: chr1-240566373; COSMIC: COSV60423738; COSMIC: COSV60423738;