rs1891231

Positions:

• chr1-240152215-G-A
• chr1-240152215-G-C
• chr1-240152215-G-T

Variant summary

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

The NM_020066.5(FMN2):​c.1783-25706G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,218 control chromosomes in the GnomAD database, including 6,385 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 0.27 (6385 hom., cov: 30)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN2	NM_020066.5	c.1783-25706G>A		intron_variant		ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.1783-25706G>A		intron_variant		5	NM_020066.5	ENSP00000318884	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40562 AN: 151100 Hom.: 6387 Cov.: 30

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.268 AC: 40562 AN: 151218 Hom.: 6385 Cov.: 30 AF XY: 0.272 AC XY: 20069 AN XY: 73758

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.289

Alfa AF: 0.322 Hom.: 16379

Bravo AF: 0.263

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.27

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: rs1891231; hg19: chr1-240315515;