rs71818992

Variant names:

• chr15-32776688-T-TTC
• rs71818992
• NM_001277313.2:c.4215+146_4215+147insGA

Your query was ambiguous. Multiple possible variants found:

• chr15-32776688-T-TTC
• chr15-32776688-T-TTCTTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001277313.2(FMN1):​c.4215+146_4215+147insGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 184,950 control chromosomes in the GnomAD database, including 1,493 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1340 hom., cov: 26)
  • Exomes 𝑓: 0.49 (153 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.641
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-32776688-T-TTC is Benign according to our data. Variant chr15-32776688-T-TTC is described in ClinVar as Benign. ClinVar VariationId is 1275586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 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.4215+146_4215+147insGA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+146_3546+147insGA		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.4215+146_4215+147insGA		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3546+146_3546+147insGA		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3921+146_3921+147insGA		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes AF: 0.154 AC: 19626 AN: 127388 Hom.: 1340 Cov.: 26

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0585

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.486 AC: 27970 AN: 57558 Hom.: 153 AF XY: 0.485 AC XY: 14455 AN XY: 29806

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

African (AFR) AF: 0.479 AC: 854 AN: 1784

American (AMR) AF: 0.484 AC: 879 AN: 1816

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 991 AN: 2006

East Asian (EAS) AF: 0.485 AC: 2228 AN: 4594

South Asian (SAS) AF: 0.483 AC: 2077 AN: 4304

European-Finnish (FIN) AF: 0.489 AC: 2127 AN: 4348

Middle Eastern (MID) AF: 0.435 AC: 214 AN: 492

European-Non Finnish (NFE) AF: 0.486 AC: 16901 AN: 34742

Other (OTH) AF: 0.489 AC: 1699 AN: 3472

⚠️ 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: 0.154 AC: 19640 AN: 127392 Hom.: 1340 Cov.: 26 AF XY: 0.155 AC XY: 9472 AN XY: 61292

African (AFR) AF: 0.164 AC: 5520 AN: 33666

American (AMR) AF: 0.156 AC: 1886 AN: 12062

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 525 AN: 3208

East Asian (EAS) AF: 0.210 AC: 690 AN: 3278

South Asian (SAS) AF: 0.158 AC: 621 AN: 3932

European-Finnish (FIN) AF: 0.169 AC: 1263 AN: 7452

Middle Eastern (MID) AF: 0.220 AC: 55 AN: 250

European-Non Finnish (NFE) AF: 0.143 AC: 8731 AN: 60932

Other (OTH) AF: 0.170 AC: 299 AN: 1758

Alfa AF: 0.0179 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71818992; hg19: chr15-33068889; COSMIC: COSV105231015;