15-32776687-CTTTTTTTTTT-CTTTTTTT

Variant names:

• chr15-32776687-CTTT-C
• rs34593790
• NM_001277313.2:c.4215+145_4215+147delAAA

Variant summary

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

The NM_001277313.2(FMN1):​c.4215+145_4215+147delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 447,696 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 0.000057 (0 hom., cov: 26)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• 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 AMR (0.0177) population. However there is too low homozygotes in high coverage region: (expected more than 11, 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+145_4215+147delAAA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+145_3546+147delAAA		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+145_4215+147delAAA		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3546+145_3546+147delAAA		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3921+145_3921+147delAAA		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.0000572 AC: 7 AN: 122358 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000812

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000454

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0141 AC: 4588 AN: 325338 Hom.: 0 AF XY: 0.0142 AC XY: 2432 AN XY: 171152

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

African (AFR) AF: 0.0142 AC: 126 AN: 8868

American (AMR) AF: 0.0198 AC: 215 AN: 10846

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 138 AN: 10268

East Asian (EAS) AF: 0.0180 AC: 420 AN: 23370

South Asian (SAS) AF: 0.0177 AC: 470 AN: 26626

European-Finnish (FIN) AF: 0.0125 AC: 289 AN: 23148

Middle Eastern (MID) AF: 0.0113 AC: 22 AN: 1954

European-Non Finnish (NFE) AF: 0.0130 AC: 2621 AN: 201106

Other (OTH) AF: 0.0150 AC: 287 AN: 19152

⚠️ 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: 0.0000572 AC: 7 AN: 122358 Hom.: 0 Cov.: 26 AF XY: 0.0000680 AC XY: 4 AN XY: 58860

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

African (AFR) AF: 0.0000636 AC: 2 AN: 31462

American (AMR) AF: 0.0000812 AC: 1 AN: 12314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2920

East Asian (EAS) AF: 0.000454 AC: 2 AN: 4408

South Asian (SAS) AF: 0.00 AC: 0 AN: 3844

European-Finnish (FIN) AF: 0.000286 AC: 2 AN: 6988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57772

Other (OTH) AF: 0.00 AC: 0 AN: 1590

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000103377), 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		0.75
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;