Variant rs12981131 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.2418+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,589,288 control chromosomes in the GnomAD database, including 3,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 317 hom., cov: 31)

Exomes 𝑓: 0.066 ( 3466 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.499

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:

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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=-0.86).

BP6

Variant 19-38728054-A-G is Benign according to our data. Variant chr19-38728054-A-G is described in ClinVar as [Benign]. Clinvar id is 1250001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0892 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.2418+28A>G		intron_variant		ENST00000252699.7	NP_004915.2
LOC107985291	XR_001753937.2 linkuse as main transcript	n.169+134T>C		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.2418+28A>G		intron_variant		1	NM_004924.6	ENSP00000252699	A1	O43707-1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9589

AN:

151470

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0717

Gnomad AMI

AF:

0.00662

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.0584

Gnomad EAS

AF:

0.0464

Gnomad SAS

AF:

0.0970

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0769

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0599

GnomAD3 exomes

AF:

0.0658

AC:

13730

AN:

208672

Hom.:

503

AF XY:

0.0671

AC XY:

7579

AN XY:

112878

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.0705

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.0395

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0702

GnomAD4 exome

AF:

0.0663

AC:

95290

AN:

1437700

Hom.:

3466

Cov.:

AF XY:

0.0672

AC XY:

47922

AN XY:

713388

show subpopulations

Gnomad4 AFR exome

AF:

0.0700

Gnomad4 AMR exome

AF:

0.0730

Gnomad4 ASJ exome

AF:

0.0632

Gnomad4 EAS exome

AF:

0.0456

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0305

Gnomad4 NFE exome

AF:

0.0657

Gnomad4 OTH exome

AF:

0.0668

GnomAD4 genome

AF:

0.0633

AC:

9589

AN:

151588

Hom.:

317

Cov.:

AF XY:

0.0622

AC XY:

4605

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.0715

Gnomad4 AMR

AF:

0.0636

Gnomad4 ASJ

AF:

0.0584

Gnomad4 EAS

AF:

0.0465

Gnomad4 SAS

AF:

0.0964

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.0639

Gnomad4 OTH

AF:

0.0607

Alfa

AF:

0.0371

Hom.:

Bravo

AF:

0.0664

Asia WGS

AF:

0.0910

AC:

315

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

-0.86

CADD

Benign

1.9

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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