15-32774277-C-T

Variant names:

• chr15-32774277-C-T
• rs16958712
• NM_001277313.2:c.*33G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277313.2(FMN1):​c.*33G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,558,092 control chromosomes in the GnomAD database, including 13,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1409 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12098 hom.)
• Consequence: FMN1 NM_001277313.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.712
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-32774277-C-T is Benign according to our data. Variant chr15-32774277-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

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.*33G>A		3_prime_UTR	Exon 21 of 21	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.*33G>A		3_prime_UTR	Exon 17 of 17	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.*33G>A		3_prime_UTR	Exon 21 of 21	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.*33G>A		3_prime_UTR	Exon 17 of 17	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.*33G>A		3_prime_UTR	Exon 16 of 16	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20198 AN: 152062 Hom.: 1408 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.127 AC: 27869 AN: 218698 AF XY: 0.128

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.128 AC: 180633 AN: 1405912 Hom.: 12098 Cov.: 24 AF XY: 0.129 AC XY: 89840 AN XY: 699102

African (AFR) AF: 0.134 AC: 4357 AN: 32462

American (AMR) AF: 0.123 AC: 5161 AN: 41964

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3872 AN: 25510

East Asian (EAS) AF: 0.132 AC: 5155 AN: 39100

South Asian (SAS) AF: 0.125 AC: 10156 AN: 81572

European-Finnish (FIN) AF: 0.138 AC: 7203 AN: 52338

Middle Eastern (MID) AF: 0.176 AC: 995 AN: 5664

European-Non Finnish (NFE) AF: 0.127 AC: 135907 AN: 1068770

Other (OTH) AF: 0.134 AC: 7827 AN: 58532

GnomAD4 genome AF: 0.133 AC: 20222 AN: 152180 Hom.: 1409 Cov.: 32 AF XY: 0.132 AC XY: 9830 AN XY: 74404

African (AFR) AF: 0.140 AC: 5823 AN: 41528

American (AMR) AF: 0.125 AC: 1909 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3470

East Asian (EAS) AF: 0.129 AC: 668 AN: 5174

South Asian (SAS) AF: 0.132 AC: 634 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1488 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8753 AN: 67992

Other (OTH) AF: 0.146 AC: 309 AN: 2110

Alfa AF: 0.134 Hom.: 1702

Bravo AF: 0.135

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.57
PhyloP100		-0.71
Mutation Taster		=100/0	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: rs16958712; hg19: chr15-33066478; COSMIC: COSV57922404; COSMIC: COSV57922404;