15-32798878-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277313.2(FMN1):c.4056T>C(p.Phe1352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,612,918 control chromosomes in the GnomAD database, including 16,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1840 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15096 hom.)
• Consequence: FMN1 NM_001277313.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.79

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 15-32798878-A-G is Benign according to our data. Variant chr15-32798878-A-G is described in ClinVar as [Benign]. Clinvar id is 1264971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4056T>C	p.Phe1352=	synonymous_variant	19/21	ENST00000616417.5
LOC107984089	XR_002957769.2	n.198-12040A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4056T>C	p.Phe1352=	synonymous_variant	19/21	5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23365 AN: 151886 Hom.: 1839 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.140 AC: 34743 AN: 248240 Hom.: 2512 AF XY: 0.143 AC XY: 19196 AN XY: 134652

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.142 AC: 207793 AN: 1460916 Hom.: 15096 Cov.: 32 AF XY: 0.143 AC XY: 103975 AN XY: 726724

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.154 AC: 23374 AN: 152002 Hom.: 1840 Cov.: 32 AF XY: 0.152 AC XY: 11320 AN XY: 74304

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.153

Alfa AF: 0.147 Hom.: 3231

Bravo AF: 0.155

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	6.6
Dann	Benign	0.65

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: rs7162695; hg19: chr15-33091079; COSMIC: COSV57922413;