rs10495454

Variant names:

• chr1-240027925-G-A
• rs10495454
• ENST00000447095.5:c.-133+13490G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-240027925-G-A
• chr1-240027925-G-T

Variant summary

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

The ENST00000447095.5(FMN2):​c.-133+13490G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,130 control chromosomes in the GnomAD database, including 1,419 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 0.099 (1419 hom., cov: 32)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 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+13490G>A		intron_variant	Intron 1 of 6	3		ENSP00000409308.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15004 AN: 152012 Hom.: 1415 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0988 AC: 15025 AN: 152130 Hom.: 1419 Cov.: 32 AF XY: 0.0974 AC XY: 7241 AN XY: 74362

African (AFR) AF: 0.240 AC: 9939 AN: 41460

American (AMR) AF: 0.0522 AC: 799 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3468

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

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4828

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0382 AC: 2600 AN: 68006

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0538 Hom.: 384

Bravo AF: 0.106

Asia WGS AF: 0.108 AC: 373 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs10495454; hg19: chr1-240191225;