Genetic Variant NM_001277313.2:c.4216-27A>T (chr15-32774381-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

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 (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.075 ( 518 hom., cov: 32)

Exomes 𝑓: 0.094 ( 6839 hom. )

Consequence

FMN1
NM_001277313.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.881

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
FMN1	NM_001277313.2 link	c.4216-27A>T		intron_variant	Intron 20 of 20	ENST00000616417.5	NP_001264242.1	Q68DA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5 link	c.4216-27A>T		intron_variant	Intron 20 of 20	5	NM_001277313.2	ENSP00000479134.1		Q68DA7-1

Frequencies

GnomAD3 genomes

AF:

0.0752

AC:

11443

AN:

152124

Hom.:

517

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0926

AC XY:

63611

AN XY:

686996

show subpopulations

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.:

AF XY:

0.0724

AC XY:

5389

AN XY:

74438

show subpopulations

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:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

DANN

Benign

0.72

BranchPoint Hunter

2.0

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

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