NM_001277313.2:c.4216-27A>T

Variant names:

• chr15-32774381-T-A
• rs28569405
• NM_001277313.2:c.4216-27A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277313.2(FMN1):​c.4216-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,540,498 control chromosomes in the GnomAD database, including 7,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.075 (518 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6839 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.881
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-32774381-T-A is Benign according to our data. Variant chr15-32774381-T-A is described in ClinVar as Benign. ClinVar VariationId is 1267922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 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.4216-27A>T		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3547-27A>T		intron	N/A	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.4216-27A>T		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3547-27A>T		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3922-27A>T		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11443 AN: 152124 Hom.: 517 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0949

GnomAD2 exomes AF: 0.0783 AC: 13122 AN: 167642 AF XY: 0.0771

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.0676

Gnomad ASJ exome AF: 0.0897

Gnomad EAS exome AF: 0.000242

Gnomad FIN exome AF: 0.0978

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0888

GnomAD4 exome AF: 0.0944 AC: 131107 AN: 1388256 Hom.: 6839 Cov.: 25 AF XY: 0.0926 AC XY: 63611 AN XY: 686996

African (AFR) AF: 0.0326 AC: 1024 AN: 31372

American (AMR) AF: 0.0682 AC: 2319 AN: 34010

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 2258 AN: 24894

East Asian (EAS) AF: 0.000212 AC: 8 AN: 37810

South Asian (SAS) AF: 0.0205 AC: 1590 AN: 77738

European-Finnish (FIN) AF: 0.0940 AC: 4760 AN: 50650

Middle Eastern (MID) AF: 0.119 AC: 674 AN: 5642

European-Non Finnish (NFE) AF: 0.106 AC: 113209 AN: 1068518

Other (OTH) AF: 0.0914 AC: 5265 AN: 57622

GnomAD4 genome AF: 0.0752 AC: 11451 AN: 152242 Hom.: 518 Cov.: 32 AF XY: 0.0724 AC XY: 5389 AN XY: 74438

African (AFR) AF: 0.0325 AC: 1351 AN: 41552

American (AMR) AF: 0.0812 AC: 1241 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4826

European-Finnish (FIN) AF: 0.0999 AC: 1060 AN: 10614

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7123 AN: 67998

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0924 Hom.: 135

Bravo AF: 0.0731

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.72
PhyloP100		0.88
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28569405; hg19: chr15-33066582;