19-38676720-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004924.6(ACTN4):​c.163-23880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,932 control chromosomes in the GnomAD database, including 21,186 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21186 hom., cov: 31)

Consequence

ACTN4
NM_004924.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.848
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACTN4NM_004924.6 linkc.163-23880A>G intron_variant Intron 1 of 20 ENST00000252699.7 NP_004915.2 O43707-1A0A0S2Z3G9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTN4ENST00000252699.7 linkc.163-23880A>G intron_variant Intron 1 of 20 1 NM_004924.6 ENSP00000252699.2 O43707-1

Frequencies

GnomAD3 genomes
AF:
0.523
AC:
79450
AN:
151814
Hom.:
21176
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.435
Gnomad AMI
AF:
0.529
Gnomad AMR
AF:
0.494
Gnomad ASJ
AF:
0.494
Gnomad EAS
AF:
0.614
Gnomad SAS
AF:
0.658
Gnomad FIN
AF:
0.567
Gnomad MID
AF:
0.363
Gnomad NFE
AF:
0.563
Gnomad OTH
AF:
0.502
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.523
AC:
79494
AN:
151932
Hom.:
21186
Cov.:
31
AF XY:
0.525
AC XY:
38980
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.435
Gnomad4 AMR
AF:
0.493
Gnomad4 ASJ
AF:
0.494
Gnomad4 EAS
AF:
0.615
Gnomad4 SAS
AF:
0.657
Gnomad4 FIN
AF:
0.567
Gnomad4 NFE
AF:
0.563
Gnomad4 OTH
AF:
0.506
Alfa
AF:
0.557
Hom.:
13371
Bravo
AF:
0.511
Asia WGS
AF:
0.644
AC:
2239
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.50
DANN
Benign
0.61

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.

Other links and lift over

dbSNP: rs755690; hg19: chr19-39167360; API