Genetic Variant FMN1:c.4215+146_4215+147insGA (chr15-32776688-T-TTC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001277313.2(FMN1):c.4215+146_4215+147insGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 184,950 control chromosomes in the GnomAD database, including 1,493 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1340 hom., cov: 26)

Exomes 𝑓: 0.49 ( 153 hom. )

Consequence

FMN1
NM_001277313.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.641

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-32776688-T-TTC is Benign according to our data. Variant chr15-32776688-T-TTC is described in ClinVar as Benign. ClinVar VariationId is 1275586.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 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+146_4215+147insGA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+146_3546+147insGA		intron	N/A	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4215+146_4215+147insGA	intron	N/A	ENSP00000479134.1	Q68DA7-1
FMN1	ENST00000334528.13	TSL:1	c.3546+146_3546+147insGA	intron	N/A	ENSP00000333950.9	Q68DA7-5
FMN1	ENST00000561249.5	TSL:5	c.3921+146_3921+147insGA	intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

19626

AN:

127388

Hom.:

1340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0585

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.486

AC:

27970

AN:

57558

Hom.:

153

AF XY:

0.485

AC XY:

14455

AN XY:

29806

show subpopulations

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

African (AFR)

AF:

0.479

AC:

854

AN:

1784

American (AMR)

AF:

0.484

AC:

879

AN:

1816

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

991

AN:

2006

East Asian (EAS)

AF:

0.485

AC:

2228

AN:

4594

South Asian (SAS)

AF:

0.483

AC:

2077

AN:

4304

European-Finnish (FIN)

AF:

0.489

AC:

2127

AN:

4348

Middle Eastern (MID)

AF:

0.435

AC:

214

AN:

492

European-Non Finnish (NFE)

AF:

0.486

AC:

16901

AN:

34742

Other (OTH)

AF:

0.489

AC:

1699

AN:

3472

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

Heterozygous variant carriers

1130

2260

3390

4520

5650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.154

AC:

19640

AN:

127392

Hom.:

1340

Cov.:

AF XY:

0.155

AC XY:

9472

AN XY:

61292

show subpopulations

African (AFR)

AF:

0.164

AC:

5520

AN:

33666

American (AMR)

AF:

0.156

AC:

1886

AN:

12062

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

525

AN:

3208

East Asian (EAS)

AF:

0.210

AC:

690

AN:

3278

South Asian (SAS)

AF:

0.158

AC:

621

AN:

3932

European-Finnish (FIN)

AF:

0.169

AC:

1263

AN:

7452

Middle Eastern (MID)

AF:

0.220

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.143

AC:

8731

AN:

60932

Other (OTH)

AF:

0.170

AC:

299

AN:

1758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

802

1603

2405

3206

4008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0179

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over