19-38683692-G-A

Position:

• chr19-38683692-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004924.6(ACTN4):​c.163-16908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,274 control chromosomes in the GnomAD database, including 58,651 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 0.88 (58651 hom., cov: 34)
• Consequence: ACTN4 NM_004924.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN4	NM_004924.6	c.163-16908G>A		intron_variant		ENST00000252699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN4	ENST00000252699.7	c.163-16908G>A		intron_variant		1	NM_004924.6	A1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133452 AN: 152156 Hom.: 58601 Cov.: 34

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.883

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133562 AN: 152274 Hom.: 58651 Cov.: 34 AF XY: 0.879 AC XY: 65468 AN XY: 74442

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.899

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.883

Alfa AF: 0.867 Hom.: 84199

Bravo AF: 0.879

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs973009; hg19: chr19-39174332;