Variant rs4664114 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_052905.4(FMNL2):c.120T>C(p.Asn40=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,608,258 control chromosomes in the GnomAD database, including 370,392 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34857 hom., cov: 31)

Exomes 𝑓: 0.68 ( 335535 hom. )

Consequence

FMNL2
NM_052905.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

FMNL2 (HGNC:18267): (formin like 2) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

FMNL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-152521945-T-C is Benign according to our data. Variant chr2-152521945-T-C is described in ClinVar as [Benign]. Clinvar id is 1526376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMNL2	NM_052905.4 linkuse as main transcript	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/26	ENST00000288670.14	NP_443137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14 linkuse as main transcript	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/26	1	NM_052905.4	ENSP00000288670	P1	Q96PY5-3
FMNL2	ENST00000475377.3 linkuse as main transcript	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/28	5		ENSP00000418959

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102587

AN:

151862

Hom.:

34836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.684

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.661

GnomAD3 exomes

AF:

0.694

AC:

171716

AN:

247598

Hom.:

60166

AF XY:

0.687

AC XY:

92238

AN XY:

134280

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.831

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.738

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.705

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.681

GnomAD4 exome

AF:

0.677

AC:

986407

AN:

1456278

Hom.:

335535

Cov.:

AF XY:

0.676

AC XY:

490171

AN XY:

724644

show subpopulations

Gnomad4 AFR exome

AF:

0.644

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.744

Gnomad4 SAS exome

AF:

0.682

Gnomad4 FIN exome

AF:

0.699

Gnomad4 NFE exome

AF:

0.671

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.675

AC:

102648

AN:

151980

Hom.:

34857

Cov.:

AF XY:

0.678

AC XY:

50317

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.603

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.655

Alfa

AF:

0.667

Hom.:

44726

Bravo

AF:

0.677

Asia WGS

AF:

0.682

AC:

2376

AN:

3478

EpiCase

AF:

0.658

EpiControl

AF:

0.666

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over