rs1534596

Positions:

• chr15-32822681-A-C
• chr15-32822681-A-T

Variant summary

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

The NM_001277313.2(FMN1):​c.3929-18349T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,948 control chromosomes in the GnomAD database, including 11,460 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 0.37 (11460 hom., cov: 32)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.3929-18349T>G		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.3929-18349T>G		intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56735 AN: 151830 Hom.: 11457 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.374 AC: 56773 AN: 151948 Hom.: 11460 Cov.: 32 AF XY: 0.378 AC XY: 28037 AN XY: 74268

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.385

Alfa AF: 0.371 Hom.: 6618

Bravo AF: 0.371

Asia WGS AF: 0.650 AC: 2257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.88

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: rs1534596; hg19: chr15-33114882;