rs1890025

Positions:

• chr1-240021626-A-G
• chr1-240021626-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000447095.5(FMN2):​c.-133+7191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0070 (14 hom., cov: 17)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (747/107064) while in subpopulation AFR AF= 0.0185 (480/25962). AF 95% confidence interval is 0.0171. There are 14 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.-133+7191A>G		intron_variant		3		ENSP00000409308

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 746 AN: 107040 Hom.: 14 Cov.: 17

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00255

Gnomad AMR AF: 0.00424

Gnomad ASJ AF: 0.00252

Gnomad EAS AF: 0.00592

Gnomad SAS AF: 0.00777

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00757

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

GnomAD4 genome AF: 0.00698 AC: 747 AN: 107064 Hom.: 14 Cov.: 17 AF XY: 0.00731 AC XY: 369 AN XY: 50480

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00423

Gnomad4 ASJ AF: 0.00252

Gnomad4 EAS AF: 0.00594

Gnomad4 SAS AF: 0.00751

Gnomad4 FIN AF: 0.00115

Gnomad4 NFE AF: 0.00276

Gnomad4 OTH AF: 0.00746

Alfa AF: 0.134 Hom.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1890025; hg19: chr1-240184926;