rs11553600

Positions:

chr19-38706096-G-A

Variant summary

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

The NM_004924.6(ACTN4):c.537G>A(p.Pro179=) 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 (★★).

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

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 links:

LOC107985291 (HGNC:):

LOC107985291 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=-0.49).

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. Variant chr19-38706096-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ACTN4	NM_004924.6 linkuse as main transcript	c.537G>A	p.Pro179=	synonymous_variant	5/21	ENST00000252699.7	NP_004915.2
LOC107985291	XR_001753937.2 linkuse as main transcript	n.170-3932C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN4	ENST00000252699.7 linkuse as main transcript	c.537G>A	p.Pro179=	synonymous_variant	5/21	1	NM_004924.6	ENSP00000252699	A1	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

GnomAD3 exomes

AF:

0.157

AC:

39589

AN:

251456

Hom.:

3662

AF XY:

0.163

AC XY:

22160

AN XY:

135910

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 SAS exome

AF:

0.161

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

Gnomad4 AFR exome

AF:

0.0811

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.00229

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.150

AC:

22853

AN:

152236

Hom.:

2028

Cov.:

AF XY:

0.149

AC XY:

11068

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.00812

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.177

Hom.:

1857

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 12, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.56

DANN

Benign

0.57

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