15-32776687-CTTTTTTTTTT-CTTTTTTTT

Variant names:

• chr15-32776687-CTT-C
• rs34593790
• NM_001277313.2:c.4215+146_4215+147delAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001277313.2(FMN1):​c.4215+146_4215+147delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 434,490 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 26)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.102) population. However there is too low homozygotes in high coverage region: (expected more than 428, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277313.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	NM_001277313.2	MANE Select	c.4215+146_4215+147delAA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+146_3546+147delAA		intron	N/A	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4215+146_4215+147delAA		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3546+146_3546+147delAA		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3921+146_3921+147delAA		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.000581 AC: 71 AN: 122256 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

Gnomad ASJ AF: 0.000343

Gnomad EAS AF: 0.00114

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000381

Gnomad OTH AF: 0.000630

GnomAD4 exome AF: 0.0871 AC: 27203 AN: 312224 Hom.: 0 AF XY: 0.0870 AC XY: 14283 AN XY: 164176

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0812 AC: 694 AN: 8548

American (AMR) AF: 0.0998 AC: 1042 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 832 AN: 9758

East Asian (EAS) AF: 0.105 AC: 2377 AN: 22620

South Asian (SAS) AF: 0.0880 AC: 2269 AN: 25790

European-Finnish (FIN) AF: 0.0844 AC: 1865 AN: 22094

Middle Eastern (MID) AF: 0.0665 AC: 126 AN: 1896

European-Non Finnish (NFE) AF: 0.0853 AC: 16446 AN: 192726

Other (OTH) AF: 0.0846 AC: 1552 AN: 18346

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000581 AC: 71 AN: 122266 Hom.: 0 Cov.: 26 AF XY: 0.000748 AC XY: 44 AN XY: 58826

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000159 AC: 5 AN: 31496

American (AMR) AF: 0.00130 AC: 16 AN: 12320

Ashkenazi Jewish (ASJ) AF: 0.000343 AC: 1 AN: 2918

East Asian (EAS) AF: 0.00114 AC: 5 AN: 4394

South Asian (SAS) AF: 0.00 AC: 0 AN: 3828

European-Finnish (FIN) AF: 0.00302 AC: 21 AN: 6944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 224

European-Non Finnish (NFE) AF: 0.000381 AC: 22 AN: 57734

Other (OTH) AF: 0.000627 AC: 1 AN: 1594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

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: rs34593790; hg19: chr15-33068888;