rs11553600

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004924.6(ACTN4):c.537G>A(p.Pro179Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,962 control chromosomes in the GnomAD database, including 24,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P179P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.15 ( 2028 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22850 hom. )

Consequence

ACTN4
NM_004924.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.55

Publications

15 publications found

Variant links:

Genes affected

ACTN4 (HGNC:166): (actinin alpha 4) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]

ACTN4 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACTN4 links:

ENSG00000298338 (HGNC:):

ENSG00000298338 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 19-38706096-G-A is Benign according to our data. Variant chr19-38706096-G-A is described in ClinVar as [Benign]. Clinvar id is 259581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN4	NM_004924.6 link	c.537G>A	p.Pro179Pro	synonymous_variant	Exon 5 of 21	ENST00000252699.7	NP_004915.2	O43707-1A0A0S2Z3G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN4	ENST00000252699.7 link	c.537G>A	p.Pro179Pro	synonymous_variant	Exon 5 of 21	1	NM_004924.6	ENSP00000252699.2		O43707-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22844

AN:

152118

Hom.:

2028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.00810

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.181

GnomAD2 exomes

AF:

0.157

AC:

39589

AN:

251456

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.0788

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.00386

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.172

AC:

251223

AN:

1461726

Hom.:

22850

Cov.:

AF XY:

0.173

AC XY:

126018

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.0811

AC:

2716

AN:

33480

American (AMR)

AF:

0.111

AC:

4984

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5687

AN:

26128

East Asian (EAS)

AF:

0.00229

AC:

AN:

39694

South Asian (SAS)

AF:

0.163

AC:

14032

AN:

86256

European-Finnish (FIN)

AF:

0.164

AC:

8747

AN:

53408

Middle Eastern (MID)

AF:

0.324

AC:

1866

AN:

5768

European-Non Finnish (NFE)

AF:

0.183

AC:

202978

AN:

1111878

Other (OTH)

AF:

0.168

AC:

10122

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

12164

24329

36493

48658

60822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.150

AC:

22853

AN:

152236

Hom.:

2028

Cov.:

AF XY:

0.149

AC XY:

11068

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0808

AC:

3355

AN:

41540

American (AMR)

AF:

0.157

AC:

2404

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

758

AN:

3470

East Asian (EAS)

AF:

0.00812

AC:

AN:

5174

South Asian (SAS)

AF:

0.158

AC:

763

AN:

4828

European-Finnish (FIN)

AF:

0.159

AC:

1689

AN:

10602

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13035

AN:

68002

Other (OTH)

AF:

0.180

AC:

381

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

994

1987

2981

3974

4968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.176

Hom.:

2077

Bravo

AF:

0.146

Asia WGS

AF:

0.0830

AC:

288

AN:

3476

EpiCase

AF:

0.213

EpiControl

AF:

0.210

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 28. Only high quality variants are reported. -

Focal segmental glomerulosclerosis 1

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.56

(source)

DANN

Benign

0.57

PhyloP100

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11553600

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over