rs12593223

Variant names:

• chr15-32800761-G-A
• rs12593223
• NM_001277313.2:c.3981-1808C>T

Variant summary

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

The NM_001277313.2(FMN1):​c.3981-1808C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,192 control chromosomes in the GnomAD database, including 2,967 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 0.19 (2967 hom., cov: 33)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 5 publications found

Genes affected

FMN1 (HGNC:3768): (formin 1) This gene belongs to the formin homology family and encodes a protein that has a role in the formation of adherens junction and the polymerization of linear actin cables. The homologous gene in mouse is associated with limb deformity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

LOC107984089 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.3981-1808C>T		intron_variant	Intron 18 of 20	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.3981-1808C>T		intron_variant	Intron 18 of 20	5	NM_001277313.2	ENSP00000479134.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28944 AN: 152074 Hom.: 2959 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.190 AC: 28968 AN: 152192 Hom.: 2967 Cov.: 33 AF XY: 0.192 AC XY: 14255 AN XY: 74392

African (AFR) AF: 0.124 AC: 5131 AN: 41534

American (AMR) AF: 0.183 AC: 2797 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1030 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1952 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15104 AN: 68012

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.214 Hom.: 15462

Bravo AF: 0.186

Asia WGS AF: 0.228 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.39
PhyloP100		-0.17
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: rs12593223; hg19: chr15-33092962;