dbSNP rs11227332: CFL1:c.-74T>C (chr11-65856268-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000530413.1(CFL1):c.-74T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,599,966 control chromosomes in the GnomAD database, including 25,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1806 hom., cov: 31)

Exomes 𝑓: 0.18 ( 23514 hom. )

Consequence

CFL1
ENST00000530413.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

CFL1 (HGNC:1874): (cofilin 1) The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

CFL1 links:

SNX32 (HGNC:26423): (sorting nexin 32) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

SNX32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFL1	NM_005507.3 link	c.4-26T>C		intron_variant	Intron 1 of 3	ENST00000308162.10	NP_005498.1	P23528V9HWI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10 link	c.4-26T>C		intron_variant	Intron 1 of 3	1	NM_005507.3	ENSP00000309629.5		P23528

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21871

AN:

152086

Hom.:

1802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0737

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.149

AC:

36637

AN:

245134

Hom.:

3144

AF XY:

0.149

AC XY:

19824

AN XY:

132622

show subpopulations

Gnomad AFR exome

AF:

0.0713

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.0576

Gnomad SAS exome

AF:

0.0880

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.175

AC:

254044

AN:

1447762

Hom.:

23514

Cov.:

AF XY:

0.174

AC XY:

124798

AN XY:

718250

show subpopulations

Gnomad4 AFR exome

AF:

0.0686

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.0664

Gnomad4 SAS exome

AF:

0.0896

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.144

AC:

21885

AN:

152204

Hom.:

1806

Cov.:

AF XY:

0.139

AC XY:

10330

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0738

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.0654

Gnomad4 SAS

AF:

0.0822

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.181

Hom.:

3286

Bravo

AF:

0.141

Asia WGS

AF:

0.0720

AC:

253

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.55

BranchPoint Hunter

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over