rs1891231

Variant names:

• chr1-240152215-G-A
• rs1891231
• NM_020066.5:c.1783-25706G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

FMN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 47

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.1783-25706G>A		intron_variant	Intron 2 of 17	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.1783-25706G>A		intron_variant	Intron 2 of 17	5	NM_020066.5	ENSP00000318884.9

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

African (AFR) AF: 0.0983 AC: 4048 AN: 41194

American (AMR) AF: 0.382 AC: 5808 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1166 AN: 5136

South Asian (SAS) AF: 0.363 AC: 1735 AN: 4782

European-Finnish (FIN) AF: 0.332 AC: 3418 AN: 10290

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22290 AN: 67842

Other (OTH) AF: 0.289 AC: 607 AN: 2102

Alfa AF: 0.310 Hom.: 24582

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
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1891231; hg19: chr1-240315515;