Genetic Variant NM_001277313.2:c.4132T>C (chr15-32776918-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001277313.2(FMN1):c.4132T>C(p.Leu1378Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FMN1
NM_001277313.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0002082

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.725

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-32776918-A-G is Benign according to our data. Variant chr15-32776918-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1633281.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.725 with no splicing effect.

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.4132T>C	p.Leu1378Leu	splice_region synonymous	Exon 20 of 21	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3463T>C	p.Leu1155Leu	splice_region synonymous	Exon 16 of 17	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4132T>C	p.Leu1378Leu	splice_region synonymous	Exon 20 of 21	ENSP00000479134.1	Q68DA7-1
FMN1	ENST00000334528.13	TSL:1	c.3463T>C	p.Leu1155Leu	splice_region synonymous	Exon 16 of 17	ENSP00000333950.9	Q68DA7-5
FMN1	ENST00000561249.5	TSL:5	c.3838T>C	p.Leu1280Leu	splice_region synonymous	Exon 15 of 16	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1419346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32786

American (AMR)

AF:

0.00

AC:

AN:

40708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25506

East Asian (EAS)

AF:

0.00

AC:

AN:

39094

South Asian (SAS)

AF:

0.00

AC:

AN:

81678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1082928

Other (OTH)

AF:

0.00

AC:

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.8

(source)

DANN

Benign

0.75

PhyloP100

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.018

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over