15-33016220-C-G

Variant names:

• chr15-33016220-C-G
• rs10519774
• NM_001277313.2:c.2162-8145G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.2162-8145G>C		intron_variant	Intron 6 of 20	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.2162-8145G>C		intron_variant	Intron 6 of 20	5	NM_001277313.2	ENSP00000479134.1
FMN1	ENST00000334528.13	c.1493-8145G>C		intron_variant	Intron 2 of 16	1		ENSP00000333950.9
FMN1	ENST00000561249.5	c.1868-8145G>C		intron_variant	Intron 1 of 15	5		ENSP00000453443.1
FMN1	ENST00000672206.1	c.428-8145G>C		intron_variant	Intron 3 of 17			ENSP00000500647.1

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

African (AFR) AF: 0.173 AC: 7176 AN: 41514

American (AMR) AF: 0.208 AC: 3177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3472

East Asian (EAS) AF: 0.170 AC: 881 AN: 5188

South Asian (SAS) AF: 0.193 AC: 930 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1812 AN: 10558

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12825 AN: 67980

Other (OTH) AF: 0.170 AC: 358 AN: 2112

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
PhyloP100		-0.71
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10519774; hg19: chr15-33308421;