rs10495455

Variant names:

• chr1-240028354-C-T
• rs10495455
• ENST00000447095.5:c.-133+13919C>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+13919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,058 control chromosomes in the GnomAD database, including 3,848 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 0.21 (3848 hom., cov: 32)
• Consequence: FMN2 ENST00000447095.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 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+13919C>T		intron_variant	Intron 1 of 6	3		ENSP00000409308.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32451 AN: 151940 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.213 AC: 32451 AN: 152058 Hom.: 3848 Cov.: 32 AF XY: 0.211 AC XY: 15652 AN XY: 74322

African (AFR) AF: 0.148 AC: 6154 AN: 41510

American (AMR) AF: 0.178 AC: 2714 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3466

East Asian (EAS) AF: 0.0546 AC: 283 AN: 5182

South Asian (SAS) AF: 0.202 AC: 973 AN: 4812

European-Finnish (FIN) AF: 0.234 AC: 2468 AN: 10566

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17964 AN: 67936

Other (OTH) AF: 0.230 AC: 485 AN: 2106

Alfa AF: 0.220 Hom.: 699

Bravo AF: 0.206

Asia WGS AF: 0.116 AC: 404 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.69
DANN	Benign	0.70
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10495455; hg19: chr1-240191654;