Variant 19-38724693-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004924.6(ACTN4):c.2010+128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,461,304 control chromosomes in the GnomAD database, including 151,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 12198 hom., cov: 32)

Exomes 𝑓: 0.45 ( 139235 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.362

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-38724693-C-T is Benign according to our data. Variant chr19-38724693-C-T is described in ClinVar as [Benign]. Clinvar id is 1183403.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN4	NM_004924.6 linkuse as main transcript	c.2010+128C>T		intron_variant		ENST00000252699.7
LOC107985291	XR_001753937.2 linkuse as main transcript	n.169+3495G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN4	ENST00000252699.7 linkuse as main transcript	c.2010+128C>T		intron_variant		1	NM_004924.6	A1	O43707-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58203

AN:

151984

Hom.:

12207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.369

GnomAD4 exome

AF:

0.455

AC:

595580

AN:

1309202

Hom.:

139235

AF XY:

0.453

AC XY:

296777

AN XY:

655540

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.393

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.477

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.383

AC:

58188

AN:

152102

Hom.:

12198

Cov.:

AF XY:

0.382

AC XY:

28418

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.498

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.423

Hom.:

2232

Bravo

AF:

0.362

Asia WGS

AF:

0.339

AC:

1179

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

DANN

Benign

0.58

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