rs10926111

Positions:

• chr1-240063521-T-C
• chr1-240063521-T-G

Variant summary

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

The ENST00000447095.5(FMN2):​c.-132-4507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,938 control chromosomes in the GnomAD database, including 17,923 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 (17923 hom., cov: 32)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 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.-132-4507T>C		intron_variant		3		ENSP00000409308

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72684 AN: 151820 Hom.: 17915 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.479 AC: 72718 AN: 151938 Hom.: 17923 Cov.: 32 AF XY: 0.480 AC XY: 35663 AN XY: 74240

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.480

Alfa AF: 0.505 Hom.: 3135

Bravo AF: 0.487

Asia WGS AF: 0.346 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10926111; hg19: chr1-240226821;