Variant rs2306196 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.820-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,145,718 control chromosomes in the GnomAD database, including 1,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 161 hom., cov: 33)

Exomes 𝑓: 0.049 ( 1385 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.960

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=-0.71).

BP6

Variant 19-38714375-C-T is Benign according to our data. Variant chr19-38714375-C-T is described in ClinVar as [Benign]. Clinvar id is 1182437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 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.820-94C>T		intron_variant		ENST00000252699.7	NP_004915.2
LOC107985291	XR_001753937.2 linkuse as main transcript	n.170-12211G>A		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.820-94C>T		intron_variant		1	NM_004924.6	ENSP00000252699	A1	O43707-1

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5922

AN:

152142

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00888

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0300

Gnomad SAS

AF:

0.0337

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.0383

GnomAD4 exome

AF:

0.0493

AC:

49011

AN:

993458

Hom.:

1385

AF XY:

0.0482

AC XY:

24605

AN XY:

510416

show subpopulations

Gnomad4 AFR exome

AF:

0.00718

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.0377

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.0641

Gnomad4 NFE exome

AF:

0.0547

Gnomad4 OTH exome

AF:

0.0478

GnomAD4 genome

AF:

0.0389

AC:

5918

AN:

152260

Hom.:

161

Cov.:

AF XY:

0.0393

AC XY:

2924

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00886

Gnomad4 AMR

AF:

0.0290

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.0299

Gnomad4 SAS

AF:

0.0335

Gnomad4 FIN

AF:

0.0708

Gnomad4 NFE

AF:

0.0561

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0493

Hom.:

Bravo

AF:

0.0339

Asia WGS

AF:

0.0420

AC:

146

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

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

-0.71

CADD

Benign

5.3

DANN

Benign

0.61

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