Variant 14-34711940-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138638.5(CFL2):c.*925T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 454,002 control chromosomes in the GnomAD database, including 11,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5973 hom., cov: 33)

Exomes 𝑓: 0.18 ( 5939 hom. )

Consequence

CFL2
NM_138638.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.241

Variant links:

Genes affected

CFL2 (HGNC:1875): (cofilin 2) This gene encodes an intracellular protein that is involved in the regulation of actin-filament dynamics. This protein is a major component of intranuclear and cytoplasmic actin rods. It can bind G- and F-actin in a 1:1 ratio of cofilin to actin, and it reversibly controls actin polymerization and depolymerization in a pH-dependent manner. Mutations in this gene cause nemaline myopathy type 7, a form of congenital myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

CFL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-34711940-A-G is Benign according to our data. Variant chr14-34711940-A-G is described in ClinVar as [Benign]. Clinvar id is 313088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL2	NM_138638.5 linkuse as main transcript	c.*925T>C		3_prime_UTR_variant	4/4	ENST00000298159.11	NP_619579.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL2	ENST00000298159.11 linkuse as main transcript	c.*925T>C	3_prime_UTR_variant	4/4	1	NM_138638.5	ENSP00000298159	P1	Q9Y281-1
CFL2	ENST00000341223.8 linkuse as main transcript	c.*925T>C	3_prime_UTR_variant	4/4	1		ENSP00000340635	P1	Q9Y281-1
CFL2	ENST00000672517.1 linkuse as main transcript	c.*925T>C	3_prime_UTR_variant	5/5			ENSP00000500532	P1	Q9Y281-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37341

AN:

151992

Hom.:

5968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.191

AC:

26009

AN:

136410

Hom.:

2966

AF XY:

0.194

AC XY:

14370

AN XY:

74072

show subpopulations

Gnomad AFR exome

AF:

0.470

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.184

AC:

55527

AN:

301892

Hom.:

5939

Cov.:

AF XY:

0.191

AC XY:

32847

AN XY:

172042

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.246

AC:

37385

AN:

152110

Hom.:

5973

Cov.:

AF XY:

0.243

AC XY:

18084

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.457

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.189

Hom.:

845

Bravo

AF:

0.253

Asia WGS

AF:

0.240

AC:

836

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nemaline myopathy 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.9

DANN

Benign

0.63

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