rs11858145

Positions:

• chr15-33067373-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000334528.13(FMN1):​c.512G>T​(p.Gly171Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,613,658 control chromosomes in the GnomAD database, including 352,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32801 hom., cov: 31)
  • Exomes 𝑓: 0.66 (319433 hom.)
• Consequence: FMN1 ENST00000334528.13 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.736

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]

LOC124903459 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.604586E-7).
• BP6: Variant 15-33067373-C-A is Benign according to our data. Variant chr15-33067373-C-A is described in ClinVar as [Benign]. Clinvar id is 1231319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.2044-2299G>T		intron_variant		ENST00000616417.5	NP_001264242.1
LOC124903459	XR_007064574.1	n.476C>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.2044-2299G>T		intron_variant		5	NM_001277313.2	ENSP00000479134	A2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99167 AN: 151864 Hom.: 32774 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.675

GnomAD3 exomes AF: 0.701 AC: 174559 AN: 249028 Hom.: 62257 AF XY: 0.701 AC XY: 94746 AN XY: 135074

Gnomad AFR exome AF: 0.597

Gnomad AMR exome AF: 0.818

Gnomad ASJ exome AF: 0.738

Gnomad EAS exome AF: 0.834

Gnomad SAS exome AF: 0.797

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.687

GnomAD4 exome AF: 0.658 AC: 961820 AN: 1461676 Hom.: 319433 Cov.: 68 AF XY: 0.661 AC XY: 480754 AN XY: 727122

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.654

Gnomad4 NFE exome AF: 0.633

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.653 AC: 99246 AN: 151982 Hom.: 32801 Cov.: 31 AF XY: 0.661 AC XY: 49067 AN XY: 74262

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.677

Alfa AF: 0.649 Hom.: 79566

Bravo AF: 0.657

TwinsUK AF: 0.640 AC: 2372

ALSPAC AF: 0.617 AC: 2377

ESP6500AA AF: 0.600 AC: 2309

ESP6500EA AF: 0.648 AC: 5361

ExAC AF: 0.695 AC: 83986

Asia WGS AF: 0.812 AC: 2820 AN: 3478

EpiCase AF: 0.634

EpiControl AF: 0.644

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.64
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
MetaRNN	Benign	9.6e-7	T;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0	B;B
Vest4		0.093
MPC		0.024
ClinPred		0.0012	T
GERP RS		1.0

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: rs11858145; hg19: chr15-33359574; COSMIC: COSV104638950;