rs11858145

Variant names:

• chr15-33067373-C-A
• rs11858145
• ENST00000334528.13:c.512G>T

Variant summary

Our verdict is Benign. The variant received -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. 11/15 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
• Publications: 27 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]

LOC124903459 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.2044-2299G>T		intron_variant	Intron 5 of 20	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.2044-2299G>T		intron_variant	Intron 5 of 20	5	NM_001277313.2	ENSP00000479134.1

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

GnomAD2 exomes AF: 0.701 AC: 174559 AN: 249028 AF XY: 0.701

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 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

African (AFR) AF: 0.601 AC: 20129 AN: 33478

American (AMR) AF: 0.807 AC: 36101 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 19231 AN: 26134

East Asian (EAS) AF: 0.852 AC: 33806 AN: 39700

South Asian (SAS) AF: 0.793 AC: 68437 AN: 86258

European-Finnish (FIN) AF: 0.654 AC: 34942 AN: 53398

Middle Eastern (MID) AF: 0.687 AC: 3965 AN: 5768

European-Non Finnish (NFE) AF: 0.633 AC: 704228 AN: 1111844

Other (OTH) AF: 0.679 AC: 40981 AN: 60372

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

African (AFR) AF: 0.600 AC: 24853 AN: 41432

American (AMR) AF: 0.750 AC: 11467 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2562 AN: 3472

East Asian (EAS) AF: 0.841 AC: 4332 AN: 5154

South Asian (SAS) AF: 0.798 AC: 3830 AN: 4798

European-Finnish (FIN) AF: 0.662 AC: 6979 AN: 10550

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42956 AN: 67964

Other (OTH) AF: 0.677 AC: 1428 AN: 2108

Alfa AF: 0.647 Hom.: 145681

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		-0.74
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
Mutation Taster		=98/2	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: rs11858145; hg19: chr15-33359574; COSMIC: COSV104638950;