rs12091371

chr1-240441752-G-A

Variant summary

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

The NM_020066.5(FMN2):c.5060+3542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,526 control chromosomes in the GnomAD database, including 4,018 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 0.18 (4018 hom., cov: 30)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5	c.5060+3542G>A		intron_variant		ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.5060+3542G>A		intron_variant		5	NM_020066.5	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26690 AN: 151410 Hom.: 4010 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.176 AC: 26723 AN: 151526 Hom.: 4018 Cov.: 30 AF XY: 0.174 AC XY: 12884 AN XY: 74008

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0726

Gnomad4 OTH AF: 0.167

Alfa AF: 0.0970 Hom.: 1337

Bravo AF: 0.196

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.93
Dann	Benign	0.23

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: rs12091371; hg19: chr1-240605052;