rs343913

Positions:

• chr15-33053675-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277313.2(FMN1):​c.2161+11282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 150,782 control chromosomes in the GnomAD database, including 26,272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26272 hom., cov: 30)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.2161+11282T>G		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.2161+11282T>G		intron_variant		5	NM_001277313.2	A2
FMN1	ENST00000334528.13	c.1492+11282T>G		intron_variant		1		P2
FMN1	ENST00000561249.5	c.1868-45600T>G		intron_variant		5		A2
FMN1	ENST00000672206.1	c.427+11282T>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 88646 AN: 150674 Hom.: 26240 Cov.: 30

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 88733 AN: 150782 Hom.: 26272 Cov.: 30 AF XY: 0.583 AC XY: 42951 AN XY: 73626

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.587

Alfa AF: 0.609 Hom.: 15146

Bravo AF: 0.587

Asia WGS AF: 0.413 AC: 1435 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.20

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: rs343913; hg19: chr15-33345876;