15-32776687-CTTTTTTTTTT-CTTTTTTTTTTT

Variant names:

• chr15-32776687-C-CT
• rs34593790
• NM_001277313.2:c.4215+147dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001277313.2(FMN1):​c.4215+147dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 453,788 control chromosomes in the GnomAD database, including 30 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (29 hom., cov: 29)
  • Exomes 𝑓: 0.025 (1 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0159 (1951/122394) while in subpopulation EAS AF = 0.0466 (205/4396). AF 95% confidence interval is 0.0414. There are 29 homozygotes in GnomAd4. There are 932 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

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+147dupA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+147dupA		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+147_4215+148insA		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3546+147_3546+148insA		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3921+147_3921+148insA		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 1943 AN: 122384 Hom.: 29 Cov.: 29

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.00737

Gnomad AMR AF: 0.00869

Gnomad ASJ AF: 0.00137

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.00885

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0122

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0132

GnomAD4 exome AF: 0.0248 AC: 8224 AN: 331394 Hom.: 1 AF XY: 0.0245 AC XY: 4264 AN XY: 174372

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

African (AFR) AF: 0.0281 AC: 254 AN: 9030

American (AMR) AF: 0.0213 AC: 236 AN: 11062

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 199 AN: 10462

East Asian (EAS) AF: 0.0546 AC: 1299 AN: 23802

South Asian (SAS) AF: 0.0265 AC: 715 AN: 27008

European-Finnish (FIN) AF: 0.0247 AC: 581 AN: 23510

Middle Eastern (MID) AF: 0.0207 AC: 41 AN: 1980

European-Non Finnish (NFE) AF: 0.0216 AC: 4436 AN: 205056

Other (OTH) AF: 0.0238 AC: 463 AN: 19484

⚠️ 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: 0.0159 AC: 1951 AN: 122394 Hom.: 29 Cov.: 29 AF XY: 0.0158 AC XY: 932 AN XY: 58886

African (AFR) AF: 0.0264 AC: 831 AN: 31512

American (AMR) AF: 0.00868 AC: 107 AN: 12326

Ashkenazi Jewish (ASJ) AF: 0.00137 AC: 4 AN: 2920

East Asian (EAS) AF: 0.0466 AC: 205 AN: 4396

South Asian (SAS) AF: 0.00915 AC: 35 AN: 3826

European-Finnish (FIN) AF: 0.0191 AC: 134 AN: 7004

Middle Eastern (MID) AF: 0.0134 AC: 3 AN: 224

European-Non Finnish (NFE) AF: 0.0105 AC: 605 AN: 57776

Other (OTH) AF: 0.0132 AC: 21 AN: 1596

Alfa AF: 0.00464 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;