Variant chr19-38704918-C-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.398-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,611,324 control chromosomes in the GnomAD database, including 3,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 251 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3445 hom. )

Consequence

ACTN4
NM_004924.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.466

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-38704918-C-T is Benign according to our data. Variant chr19-38704918-C-T is described in ClinVar as [Benign]. Clinvar id is 259579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38704918-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0888 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.398-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000252699.7
LOC107985291	XR_001753937.2 linkuse as main transcript	n.170-2754G>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.398-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004924.6	A1	O43707-1

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8485

AN:

152186

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0578

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0460

Gnomad SAS

AF:

0.0965

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0633

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0623

AC:

15652

AN:

251436

Hom.:

565

AF XY:

0.0639

AC XY:

8691

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.0678

Gnomad ASJ exome

AF:

0.0604

Gnomad EAS exome

AF:

0.0397

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0621

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0653

AC:

95220

AN:

1459020

Hom.:

3445

Cov.:

AF XY:

0.0662

AC XY:

48087

AN XY:

726130

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.0709

Gnomad4 ASJ exome

AF:

0.0622

Gnomad4 EAS exome

AF:

0.0453

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0251

Gnomad4 NFE exome

AF:

0.0654

Gnomad4 OTH exome

AF:

0.0652

GnomAD4 genome

AF:

0.0557

AC:

8489

AN:

152304

Hom.:

251

Cov.:

AF XY:

0.0548

AC XY:

4084

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0484

Gnomad4 AMR

AF:

0.0577

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.0461

Gnomad4 SAS

AF:

0.0960

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0633

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0635

Hom.:

303

Bravo

AF:

0.0584

Asia WGS

AF:

0.0890

AC:

308

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.83

CADD

Benign

1.9

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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