NM_001277313.2:c.4216-10dupT

Variant names:

• chr15-32774363-G-GA
• rs747880801
• NM_001277313.2:c.4216-10dupT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001277313.2(FMN1):​c.4216-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000853 in 1,522,226 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (0 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.240
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 15-32774363-G-GA is Benign according to our data. Variant chr15-32774363-G-GA is described in ClinVar as Likely_benign. ClinVar VariationId is 2756056.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277313.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	NM_001277313.2	MANE Select	c.4216-10dupT		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3547-10dupT		intron	N/A	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4216-10_4216-9insT		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3547-10_3547-9insT		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3922-10_3922-9insT		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.000241 AC: 36 AN: 149582 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000594

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00172 AC: 270 AN: 156984 AF XY: 0.00160

Gnomad AFR exome AF: 0.00201

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.000963

Gnomad EAS exome AF: 0.00148

Gnomad FIN exome AF: 0.000519

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.000920 AC: 1263 AN: 1372644 Hom.: 0 Cov.: 27 AF XY: 0.000863 AC XY: 588 AN XY: 681038

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00170 AC: 52 AN: 30584

American (AMR) AF: 0.00165 AC: 56 AN: 33930

Ashkenazi Jewish (ASJ) AF: 0.000453 AC: 11 AN: 24302

East Asian (EAS) AF: 0.000367 AC: 14 AN: 38104

South Asian (SAS) AF: 0.000830 AC: 64 AN: 77086

European-Finnish (FIN) AF: 0.000177 AC: 9 AN: 50862

Middle Eastern (MID) AF: 0.000910 AC: 5 AN: 5492

European-Non Finnish (NFE) AF: 0.000940 AC: 992 AN: 1055390

Other (OTH) AF: 0.00105 AC: 60 AN: 56894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000241 AC: 36 AN: 149582 Hom.: 0 Cov.: 32 AF XY: 0.000247 AC XY: 18 AN XY: 72896

African (AFR) AF: 0.000713 AC: 29 AN: 40654

American (AMR) AF: 0.0000663 AC: 1 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000594 AC: 4 AN: 67350

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00365 Hom.: 0

Bravo AF: 0.000242

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism

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: rs747880801; hg19: chr15-33066564; COSMIC: COSV57919522;