15-32774381-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277313.2(FMN1):c.4216-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,540,498 control chromosomes in the GnomAD database, including 7,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (518 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6839 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.881

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-32774381-T-A is Benign according to our data. Variant chr15-32774381-T-A is described in ClinVar as [Benign]. Clinvar id is 1267922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4216-27A>T		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4216-27A>T		intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11443 AN: 152124 Hom.: 517 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0949

GnomAD3 exomes AF: 0.0783 AC: 13122 AN: 167642 Hom.: 643 AF XY: 0.0771 AC XY: 6836 AN XY: 88700

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.0676

Gnomad ASJ exome AF: 0.0897

Gnomad EAS exome AF: 0.000242

Gnomad SAS exome AF: 0.0234

Gnomad FIN exome AF: 0.0978

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0888

GnomAD4 exome AF: 0.0944 AC: 131107 AN: 1388256 Hom.: 6839 Cov.: 25 AF XY: 0.0926 AC XY: 63611 AN XY: 686996

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.0682

Gnomad4 ASJ exome AF: 0.0907

Gnomad4 EAS exome AF: 0.000212

Gnomad4 SAS exome AF: 0.0205

Gnomad4 FIN exome AF: 0.0940

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0914

GnomAD4 genome AF: 0.0752 AC: 11451 AN: 152242 Hom.: 518 Cov.: 32 AF XY: 0.0724 AC XY: 5389 AN XY: 74438

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0999

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0939

Alfa AF: 0.0924 Hom.: 135

Bravo AF: 0.0731

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.7
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28569405; hg19: chr15-33066582; COSMIC: COSV104638947;