rs10495455

chr1-240028354-C-T

Variant summary

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

The ENST00000447095.5(FMN2):c.-133+13919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,058 control chromosomes in the GnomAD database, including 3,848 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 0.21 (3848 hom., cov: 32)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000447095.5	c.-133+13919C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32451 AN: 151940 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.213 AC: 32451 AN: 152058 Hom.: 3848 Cov.: 32 AF XY: 0.211 AC XY: 15652 AN XY: 74322

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.230

Alfa AF: 0.220 Hom.: 699

Bravo AF: 0.206

Asia WGS AF: 0.116 AC: 404 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.69
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495455; hg19: chr1-240191654;