NM_001277313.2:c.4056T>C

Variant names:

• chr15-32798878-A-G
• rs7162695
• NM_001277313.2:c.4056T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277313.2(FMN1):​c.4056T>C​(p.Phe1352Phe) 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:3
• Conservation: PhyloP100: 1.79
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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.4056T>C	p.Phe1352Phe	synonymous	Exon 19 of 21	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3387T>C	p.Phe1129Phe	synonymous	Exon 15 of 17	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4056T>C	p.Phe1352Phe	synonymous	Exon 19 of 21	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3387T>C	p.Phe1129Phe	synonymous	Exon 15 of 17	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3762T>C	p.Phe1254Phe	synonymous	Exon 14 of 16	ENSP00000453443.1	H0YM30

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

GnomAD2 exomes AF: 0.140 AC: 34743 AN: 248240 AF XY: 0.143

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 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

African (AFR) AF: 0.194 AC: 6483 AN: 33446

American (AMR) AF: 0.106 AC: 4741 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4363 AN: 26124

East Asian (EAS) AF: 0.105 AC: 4168 AN: 39692

South Asian (SAS) AF: 0.173 AC: 14873 AN: 86118

European-Finnish (FIN) AF: 0.130 AC: 6935 AN: 53370

Middle Eastern (MID) AF: 0.165 AC: 953 AN: 5768

European-Non Finnish (NFE) AF: 0.141 AC: 156390 AN: 1111372

Other (OTH) AF: 0.147 AC: 8887 AN: 60354

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

African (AFR) AF: 0.195 AC: 8108 AN: 41474

American (AMR) AF: 0.128 AC: 1954 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.116 AC: 598 AN: 5176

South Asian (SAS) AF: 0.175 AC: 841 AN: 4810

European-Finnish (FIN) AF: 0.136 AC: 1437 AN: 10576

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9417 AN: 67956

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.149 Hom.: 4995

Bravo AF: 0.155

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.65
PhyloP100		1.8
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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