rs2444962

Positions:

• chr15-33134566-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.1867+18482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,268 control chromosomes in the GnomAD database, including 1,674 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 0.098 (1674 hom., cov: 33)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.1867+18482C>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.1867+18482C>T		intron_variant		5	NM_001277313.2	ENSP00000479134	A2
FMN1	ENST00000561249.5	c.1867+18482C>T		intron_variant		5		ENSP00000453443	A2
FMN1	ENST00000674090.1	n.170-42363C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14850 AN: 152150 Hom.: 1669 Cov.: 33

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0976 AC: 14860 AN: 152268 Hom.: 1674 Cov.: 33 AF XY: 0.106 AC XY: 7870 AN XY: 74458

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.0641

Gnomad4 NFE AF: 0.0625

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0809 Hom.: 1025

Bravo AF: 0.105

Asia WGS AF: 0.422 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2444962; hg19: chr15-33426767;