NM_001277313.2:c.4215+147delA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001277313.2(FMN1):​c.4215+147delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 444,468 control chromosomes in the GnomAD database, including 192 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (184 hom., cov: 29)
  • Exomes 𝑓: 0.27 (8 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 15-32776687-CT-C is Benign according to our data. Variant chr15-32776687-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1256948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 5611 AN: 122292 Hom.: 184 Cov.: 29

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.00491

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0325

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0396

GnomAD4 exome AF: 0.274 AC: 88269 AN: 322168 Hom.: 8 AF XY: 0.274 AC XY: 46429 AN XY: 169534

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

African (AFR) AF: 0.258 AC: 2266 AN: 8786

American (AMR) AF: 0.277 AC: 2974 AN: 10734

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 2757 AN: 10098

East Asian (EAS) AF: 0.292 AC: 6812 AN: 23306

South Asian (SAS) AF: 0.244 AC: 6473 AN: 26580

European-Finnish (FIN) AF: 0.282 AC: 6446 AN: 22896

Middle Eastern (MID) AF: 0.220 AC: 427 AN: 1938

European-Non Finnish (NFE) AF: 0.276 AC: 54841 AN: 198948

Other (OTH) AF: 0.279 AC: 5273 AN: 18882

⚠️ 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: 0.0459 AC: 5611 AN: 122300 Hom.: 184 Cov.: 29 AF XY: 0.0495 AC XY: 2913 AN XY: 58832

African (AFR) AF: 0.0488 AC: 1536 AN: 31494

American (AMR) AF: 0.0888 AC: 1094 AN: 12316

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 46 AN: 2920

East Asian (EAS) AF: 0.190 AC: 835 AN: 4396

South Asian (SAS) AF: 0.0685 AC: 262 AN: 3824

European-Finnish (FIN) AF: 0.0737 AC: 514 AN: 6974

Middle Eastern (MID) AF: 0.0357 AC: 8 AN: 224

European-Non Finnish (NFE) AF: 0.0216 AC: 1249 AN: 57746

Other (OTH) AF: 0.0396 AC: 63 AN: 1592

Alfa AF: 0.00590 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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; COSMIC: COSV57916893;