rs16840114

Positions:

• chr1-240462131-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.5061-10241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 152,094 control chromosomes in the GnomAD database, including 418 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 0.066 (418 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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 (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN2	NM_020066.5	c.5061-10241A>G		intron_variant		ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.5061-10241A>G		intron_variant		5	NM_020066.5	ENSP00000318884	P1

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10028 AN: 151976 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0659 AC: 10026 AN: 152094 Hom.: 418 Cov.: 32 AF XY: 0.0715 AC XY: 5313 AN XY: 74352

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.0979

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0622

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0614 Hom.: 54

Bravo AF: 0.0626

Asia WGS AF: 0.0930 AC: 325 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	0.61
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: rs16840114; hg19: chr1-240625431;