15-32798901-CCTT-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_001277313.2(FMN1):c.4030_4032del(p.Lys1344del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,613,356 control chromosomes in the GnomAD database, including 1,536 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (125 hom., cov: 31)
  • Exomes 𝑓: 0.040 (1411 hom.)
• Consequence: FMN1 NM_001277313.2 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.64

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]

LOC107984089 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001277313.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 15-32798901-CCTT-C is Benign according to our data. Variant chr15-32798901-CCTT-C is described in ClinVar as [Benign]. Clinvar id is 194480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-32798901-CCTT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4030_4032del	p.Lys1344del	inframe_deletion	19/21	ENST00000616417.5
LOC107984089	XR_002957769.2	n.198-12014_198-12012del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4030_4032del	p.Lys1344del	inframe_deletion	19/21	5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5002 AN: 152126 Hom.: 123 Cov.: 31

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.0412 AC: 10239 AN: 248406 Hom.: 377 AF XY: 0.0384 AC XY: 5171 AN XY: 134778

Gnomad AFR exome AF: 0.00706

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.0267

Gnomad FIN exome AF: 0.0336

Gnomad NFE exome AF: 0.0367

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0396 AC: 57799 AN: 1461112 Hom.: 1411 AF XY: 0.0390 AC XY: 28346 AN XY: 726848

Gnomad4 AFR exome AF: 0.00642

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0283

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0365

GnomAD4 genome AF: 0.0329 AC: 5007 AN: 152244 Hom.: 125 Cov.: 31 AF XY: 0.0336 AC XY: 2504 AN XY: 74450

Gnomad4 AFR AF: 0.00862

Gnomad4 AMR AF: 0.0805

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0410

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0116 Hom.: 30

Bravo AF: 0.0339

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.0360

EpiControl AF: 0.0323

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 29, 2014

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs145013933; hg19: chr15-33091102;