rs10495468

Variant names:

• chr1-240399091-G-A
• rs10495468
• NM_020066.5:c.4910+6529G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-240399091-G-A
• chr1-240399091-G-C

Variant summary

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

The NM_020066.5(FMN2):​c.4910+6529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,860 control chromosomes in the GnomAD database, including 24,887 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 0.55 (24887 hom., cov: 30)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.4910+6529G>A		intron_variant	Intron 15 of 17	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.4910+6529G>A		intron_variant	Intron 15 of 17	5	NM_020066.5	ENSP00000318884.9

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83568 AN: 151742 Hom.: 24826 Cov.: 30

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.551 AC: 83692 AN: 151860 Hom.: 24887 Cov.: 30 AF XY: 0.545 AC XY: 40426 AN XY: 74194

African (AFR) AF: 0.784 AC: 32479 AN: 41450

American (AMR) AF: 0.535 AC: 8175 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3464

East Asian (EAS) AF: 0.657 AC: 3372 AN: 5136

South Asian (SAS) AF: 0.489 AC: 2341 AN: 4790

European-Finnish (FIN) AF: 0.354 AC: 3736 AN: 10542

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30266 AN: 67902

Other (OTH) AF: 0.535 AC: 1125 AN: 2102

Alfa AF: 0.483 Hom.: 3904

Bravo AF: 0.576

Asia WGS AF: 0.609 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.71
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: rs10495468; hg19: chr1-240562391;