rs10519765

chr15-32913223-G-A

Variant summary

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

The NM_001277313.2(FMN1):c.3227-2688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,956 control chromosomes in the GnomAD database, including 8,015 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 0.32 (8015 hom., cov: 32)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.3227-2688C>T		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.3227-2688C>T		intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48358 AN: 151838 Hom.: 7997 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.319 AC: 48407 AN: 151956 Hom.: 8015 Cov.: 32 AF XY: 0.314 AC XY: 23309 AN XY: 74252

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.302

Alfa AF: 0.335 Hom.: 15046

Bravo AF: 0.310

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.054
Dann	Benign	0.24

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: rs10519765; hg19: chr15-33205424;