Variant rs2306277 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277313.2(FMN1):c.2057T>C(p.Leu686Pro) variant causes a missense change. The variant allele was found at a frequency of 0.546 in 1,606,420 control chromosomes in the GnomAD database, including 243,334 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.52 ( 20840 hom., cov: 32)

Exomes 𝑓: 0.55 ( 222494 hom. )

Consequence

FMN1
NM_001277313.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.67

Variant links:

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]

FMN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9634964E-5).

BP6

Variant 15-33065061-A-G is Benign according to our data. Variant chr15-33065061-A-G is described in ClinVar as [Benign]. Clinvar id is 1265497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2 link	c.2057T>C	p.Leu686Pro	missense_variant	6/21	ENST00000616417.5	NP_001264242.1	Q68DA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5 link	c.2057T>C	p.Leu686Pro	missense_variant	6/21	5	NM_001277313.2	ENSP00000479134.1		Q68DA7-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78654

AN:

151910

Hom.:

20833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.528

AC:

129243

AN:

244892

Hom.:

35432

AF XY:

0.532

AC XY:

70717

AN XY:

132922

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.670

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.549

AC:

798225

AN:

1454392

Hom.:

222494

Cov.:

AF XY:

0.549

AC XY:

397064

AN XY:

723428

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.664

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.561

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.518

AC:

78694

AN:

152028

Hom.:

20840

Cov.:

AF XY:

0.516

AC XY:

38371

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.543

Gnomad4 ASJ

AF:

0.674

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.535

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.541

Alfa

AF:

0.552

Hom.:

47816

Bravo

AF:

0.516

TwinsUK

AF:

0.564

AC:

2093

ALSPAC

AF:

0.539

AC:

2076

ESP6500AA

AF:

0.461

AC:

1766

ESP6500EA

AF:

0.572

AC:

4721

ExAC

AF:

0.530

AC:

64013

Asia WGS

AF:

0.406

AC:

1415

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.034

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.050

T;.;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.068

MetaRNN

Benign

0.000030

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

N;.;N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

6.0

.;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

.;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.082

MPC

0.027

ClinPred

0.0050

GERP RS

5.1

Varity_R

0.21

gMVP

0.12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over