rs10495453

Variant names:

• chr1-240027635-G-A
• rs10495453
• ENST00000447095.5:c.-133+13200G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000447095.5(FMN2):​c.-133+13200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 152,014 control chromosomes in the GnomAD database, including 1,307 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 0.096 (1307 hom., cov: 33)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

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+13200G>A		intron_variant	Intron 1 of 6	3		ENSP00000409308.1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14516 AN: 151896 Hom.: 1304 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0752

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

GnomAD4 genome AF: 0.0956 AC: 14536 AN: 152014 Hom.: 1307 Cov.: 33 AF XY: 0.0945 AC XY: 7022 AN XY: 74312

African (AFR) AF: 0.229 AC: 9480 AN: 41418

American (AMR) AF: 0.0507 AC: 774 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3466

East Asian (EAS) AF: 0.121 AC: 626 AN: 5164

South Asian (SAS) AF: 0.0892 AC: 429 AN: 4812

European-Finnish (FIN) AF: 0.0214 AC: 226 AN: 10582

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0382 AC: 2598 AN: 67978

Other (OTH) AF: 0.0758 AC: 160 AN: 2110

Alfa AF: 0.0602 Hom.: 99

Bravo AF: 0.102

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.56
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs10495453; hg19: chr1-240190935;