15-32798683-T-G

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.4130+121A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 933,616 control chromosomes in the GnomAD database, including 30,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3999 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26153 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.104

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-32798683-T-G is Benign according to our data. Variant chr15-32798683-T-G is described in ClinVar as [Benign]. Clinvar id is 1294830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4130+121A>C		intron_variant		ENST00000616417.5
LOC107984089	XR_002957769.2	n.198-12235T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4130+121A>C		intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30637 AN: 152096 Hom.: 3997 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.248 AC: 193688 AN: 781402 Hom.: 26153 AF XY: 0.245 AC XY: 96465 AN XY: 394342

Gnomad4 AFR exome AF: 0.0440

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.201 AC: 30641 AN: 152214 Hom.: 3999 Cov.: 32 AF XY: 0.202 AC XY: 15044 AN XY: 74418

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.0256

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.195

Alfa AF: 0.156 Hom.: 344

Bravo AF: 0.196

Asia WGS AF: 0.0860 AC: 302 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	0.030
Dann	Benign	0.33

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: rs2123068; hg19: chr15-33090884;