15-32777103-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277313.2(FMN1):c.4131-184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,120 control chromosomes in the GnomAD database, including 1,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1472 hom., cov: 31)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-32777103-G-A is Benign according to our data. Variant chr15-32777103-G-A is described in ClinVar as [Benign]. Clinvar id is 1264178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4131-184C>T		intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4131-184C>T		intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20585 AN: 152002 Hom.: 1471 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.135 AC: 20612 AN: 152120 Hom.: 1472 Cov.: 31 AF XY: 0.135 AC XY: 10023 AN XY: 74380

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.152

Alfa AF: 0.132 Hom.: 325

Bravo AF: 0.138

Asia WGS AF: 0.133 AC: 462 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.3
Dann	Benign	0.54

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: rs80062147; hg19: chr15-33069304;