Variant rs2303040 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_004924.6(ACTN4):c.162+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,171,018 control chromosomes in the GnomAD database, including 151,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 11122 hom., cov: 24)

Exomes 𝑓: 0.53 ( 140046 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.69

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-38647968-T-C is Benign according to our data. Variant chr19-38647968-T-C is described in ClinVar as [Benign]. Clinvar id is 1269337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN4	NM_004924.6 link	c.162+61T>C		intron_variant	Intron 1 of 20	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.162+61T>C		intron_variant	Intron 1 of 20	1	NM_004924.6	ENSP00000252699.2		O43707-1

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

52201

AN:

126904

Hom.:

11130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.530

AC:

553190

AN:

1044060

Hom.:

140046

Cov.:

AF XY:

0.526

AC XY:

267585

AN XY:

508268

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.607

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.411

AC:

52174

AN:

126958

Hom.:

11122

Cov.:

AF XY:

0.410

AC XY:

25287

AN XY:

61750

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.366

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.311

Hom.:

796

Bravo

AF:

0.323

Asia WGS

AF:

0.302

AC:

1049

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

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 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 39. Only high quality variants are reported. -

Focal segmental glomerulosclerosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.59

DANN

Benign

0.50

RBP_binding_hub_radar

0.91

RBP_regulation_power_radar

3.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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