Variant 19-38647940-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004924.6(ACTN4):c.162+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,452,122 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0066 ( 37 hom. )

Consequence

ACTN4
NM_004924.6 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.184

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-38647940-G-A is Benign according to our data. Variant chr19-38647940-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1706702.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00472 (717/152014) while in subpopulation SAS AF= 0.0116 (56/4814). AF 95% confidence interval is 0.0092. There are 2 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 717 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN4	NM_004924.6 link	c.162+33G>A		intron_variant		ENST00000252699.7	NP_004915.2	O43707-1A0A0S2Z3G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN4	ENST00000252699.7 link	c.162+33G>A		intron_variant		1	NM_004924.6	ENSP00000252699.2		O43707-1

Frequencies

GnomAD3 genomes

AF:

0.00473

AC:

718

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000774

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00703

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00509

AC:

349

AN:

68596

Hom.:

AF XY:

0.00546

AC XY:

207

AN XY:

37928

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000989

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.00986

Gnomad FIN exome

AF:

0.00737

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00664

AC:

8630

AN:

1300108

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4302

AN XY:

636078

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.00148

Gnomad4 EAS exome

AF:

0.0000334

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.00706

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00521

GnomAD4 genome

AF:

0.00472

AC:

717

AN:

152014

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

354

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00704

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00658

Hom.:

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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