15-32774277-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277313.2(FMN1):c.*33G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,558,092 control chromosomes in the GnomAD database, including 13,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1409 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12098 hom.)
• Consequence: FMN1 NM_001277313.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-32774277-C-T is Benign according to our data. Variant chr15-32774277-C-T is described in ClinVar as [Benign]. Clinvar id is 1238013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.*33G>A		3_prime_UTR_variant	21/21	ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.*33G>A		3_prime_UTR_variant	21/21	5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20198 AN: 152062 Hom.: 1408 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.127 AC: 27869 AN: 218698 Hom.: 1806 AF XY: 0.128 AC XY: 15029 AN XY: 117118

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.128 AC: 180633 AN: 1405912 Hom.: 12098 Cov.: 24 AF XY: 0.129 AC XY: 89840 AN XY: 699102

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.133 AC: 20222 AN: 152180 Hom.: 1409 Cov.: 32 AF XY: 0.132 AC XY: 9830 AN XY: 74404

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.146

Alfa AF: 0.135 Hom.: 1081

Bravo AF: 0.135

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.60
Dann	Benign	0.57

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: rs16958712; hg19: chr15-33066478; COSMIC: COSV57922404; COSMIC: COSV57922404;