chr1-240064648-A-G

Position:

• chr1-240064648-A-G

Variant summary

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

The ENST00000447095.5(FMN2):​c.-132-3380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,752 control chromosomes in the GnomAD database, including 17,699 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 0.48 (17699 hom., cov: 31)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 (AMR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000447095.5	c.-132-3380A>G		intron_variant		3		ENSP00000409308

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72205 AN: 151630 Hom.: 17690 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.476 AC: 72239 AN: 151752 Hom.: 17699 Cov.: 31 AF XY: 0.478 AC XY: 35413 AN XY: 74132

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.478

Alfa AF: 0.475 Hom.: 35326

Bravo AF: 0.484

Asia WGS AF: 0.342 AC: 1189 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	7.9
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10495457; hg19: chr1-240227948;