Variant rs4621 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005507.3(CFL1):c.198C>T(p.Asp66Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,613,854 control chromosomes in the GnomAD database, including 328,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23663 hom., cov: 31)

Exomes 𝑓: 0.64 ( 304829 hom. )

Consequence

CFL1
NM_005507.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.96

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-65856048-G-A is Benign according to our data. Variant chr11-65856048-G-A is described in ClinVar as [Benign]. Clinvar id is 1291237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL1	NM_005507.3 link	c.198C>T	p.Asp66Asp	synonymous_variant	2/4	ENST00000308162.10	NP_005498.1	P23528V9HWI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10 link	c.198C>T	p.Asp66Asp	synonymous_variant	2/4	1	NM_005507.3	ENSP00000309629.5		P23528

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79828

AN:

151892

Hom.:

23668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.574

AC:

144299

AN:

251482

Hom.:

44606

AF XY:

0.596

AC XY:

80959

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.636

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.638

AC:

932502

AN:

1461844

Hom.:

304829

Cov.:

AF XY:

0.641

AC XY:

466053

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.636

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.700

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.525

AC:

79835

AN:

152010

Hom.:

23663

Cov.:

AF XY:

0.528

AC XY:

39251

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.706

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.610

Hom.:

12906

Bravo

AF:

0.491

Asia WGS

AF:

0.489

AC:

1703

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.689

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	clinical testing	GeneDx	Apr 26, 2019	- -
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

-0.50

CADD

Benign

6.9

DANN

Benign

0.93

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