rs10519774

Positions:

• chr15-33016220-C-G
• chr15-33016220-C-T

Variant summary

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

The NM_001277313.2(FMN1):​c.2162-8145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,130 control chromosomes in the GnomAD database, including 2,674 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 0.18 (2674 hom., cov: 33)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.2162-8145G>C		intron_variant		ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.2162-8145G>C		intron_variant		5	NM_001277313.2	ENSP00000479134	A2
FMN1	ENST00000334528.13	c.1493-8145G>C		intron_variant		1		ENSP00000333950	P2
FMN1	ENST00000561249.5	c.1868-8145G>C		intron_variant		5		ENSP00000453443	A2
FMN1	ENST00000672206.1	c.428-8145G>C		intron_variant				ENSP00000500647	A2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28036 AN: 152010 Hom.: 2671 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.184 AC: 28056 AN: 152130 Hom.: 2674 Cov.: 33 AF XY: 0.184 AC XY: 13663 AN XY: 74364

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.170

Alfa AF: 0.182 Hom.: 308

Bravo AF: 0.184

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.43

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: rs10519774; hg19: chr15-33308421;