rs1026752

Positions:

• chr15-33098466-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.1868-9492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,046 control chromosomes in the GnomAD database, including 7,139 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 0.29 (7139 hom., cov: 32)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

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 (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.1868-9492C>T		intron_variant		ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.1868-9492C>T		intron_variant		5	NM_001277313.2	ENSP00000479134.1
FMN1	ENST00000561249.5	c.1867+54582C>T		intron_variant		5		ENSP00000453443.1
FMN1	ENST00000672206.1	c.134-9492C>T		intron_variant				ENSP00000500647.1
FMN1	ENST00000674090.1	n.170-6263C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43761 AN: 151928 Hom.: 7140 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.288 AC: 43765 AN: 152046 Hom.: 7139 Cov.: 32 AF XY: 0.291 AC XY: 21618 AN XY: 74308

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.299

Alfa AF: 0.340 Hom.: 8066

Bravo AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1026752; hg19: chr15-33390667;