rs1890025

Variant names:

• chr1-240021626-A-G
• rs1890025
• ENST00000447095.5:c.-133+7191A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong 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
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000447095.5	c.-133+7191A>G		intron_variant	Intron 1 of 6	3		ENSP00000409308.1

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0185 AC: 480 AN: 25962

American (AMR) AF: 0.00423 AC: 43 AN: 10160

Ashkenazi Jewish (ASJ) AF: 0.00252 AC: 7 AN: 2780

East Asian (EAS) AF: 0.00594 AC: 25 AN: 4212

South Asian (SAS) AF: 0.00751 AC: 26 AN: 3464

European-Finnish (FIN) AF: 0.00115 AC: 5 AN: 4360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.00276 AC: 148 AN: 53668

Other (OTH) AF: 0.00746 AC: 11 AN: 1474

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs1890025; hg19: chr1-240184926;