rs1454985

Positions:

• chr15-33122265-T-C

Variant summary

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

The NM_001277313.2(FMN1):​c.1867+30783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,146 control chromosomes in the GnomAD database, including 11,079 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 0.36 (11079 hom., cov: 33)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.1867+30783A>G		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.1867+30783A>G		intron_variant		5	NM_001277313.2	A2
FMN1	ENST00000561249.5	c.1867+30783A>G		intron_variant		5		A2
FMN1	ENST00000674090.1	n.170-30062A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55501 AN: 152026 Hom.: 11075 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.365 AC: 55518 AN: 152146 Hom.: 11079 Cov.: 33 AF XY: 0.371 AC XY: 27579 AN XY: 74362

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.370

Alfa AF: 0.417 Hom.: 27633

Bravo AF: 0.350

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.3
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1454985; hg19: chr15-33414466;