Variant chr19-38728920-G-T 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.2419-76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 1,579,668 control chromosomes in the GnomAD database, including 3,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 264 hom., cov: 31)

Exomes 𝑓: 0.066 ( 3413 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0660

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=-0.84).

BP6

Variant 19-38728920-G-T is Benign according to our data. Variant chr19-38728920-G-T is described in ClinVar as [Benign]. Clinvar id is 1246606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0882 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.2419-76G>T		intron_variant		ENST00000252699.7	NP_004915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN4	ENST00000252699.7 linkuse as main transcript	c.2419-76G>T		intron_variant		1	NM_004924.6	ENSP00000252699	A1	O43707-1

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8677

AN:

152130

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.0457

Gnomad SAS

AF:

0.0959

Gnomad FIN

AF:

0.0259

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0580

GnomAD4 exome

AF:

0.0657

AC:

93851

AN:

1427420

Hom.:

3413

AF XY:

0.0667

AC XY:

47501

AN XY:

711902

show subpopulations

Gnomad4 AFR exome

AF:

0.0515

Gnomad4 AMR exome

AF:

0.0729

Gnomad4 ASJ exome

AF:

0.0633

Gnomad4 EAS exome

AF:

0.0457

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0304

Gnomad4 NFE exome

AF:

0.0655

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0570

AC:

8681

AN:

152248

Hom.:

264

Cov.:

AF XY:

0.0562

AC XY:

4181

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0501

Gnomad4 AMR

AF:

0.0613

Gnomad4 ASJ

AF:

0.0579

Gnomad4 EAS

AF:

0.0458

Gnomad4 SAS

AF:

0.0954

Gnomad4 FIN

AF:

0.0259

Gnomad4 NFE

AF:

0.0638

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0536

Hom.:

Bravo

AF:

0.0595

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.39

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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