rs2306197

chr19-38721760-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004924.6(ACTN4):c.1442+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,591,890 control chromosomes in the GnomAD database, including 1,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (135 hom., cov: 33)
  • Exomes 𝑓: 0.015 (1324 hom.)
• Consequence: ACTN4 NM_004924.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.82

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]

LOC107985291 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-38721760-C-T is Benign according to our data. Variant chr19-38721760-C-T is described in ClinVar as [Benign]. Clinvar id is 1248068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN4	NM_004924.6	c.1442+72C>T		intron_variant		ENST00000252699.7
LOC107985291	XR_001753937.2	n.169+6428G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN4	ENST00000252699.7	c.1442+72C>T		intron_variant		1	NM_004924.6	A1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3072 AN: 152232 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.0210

GnomAD3 exomes AF: 0.0344 AC: 7602 AN: 221140 Hom.: 533 AF XY: 0.0391 AC XY: 4736 AN XY: 121200

Gnomad AFR exome AF: 0.0302

Gnomad AMR exome AF: 0.00433

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.0123

Gnomad NFE exome AF: 0.00241

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0148 AC: 21371 AN: 1439540 Hom.: 1324 Cov.: 30 AF XY: 0.0184 AC XY: 13151 AN XY: 716240

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00956

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.00182

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0203 AC: 3086 AN: 152350 Hom.: 135 Cov.: 33 AF XY: 0.0234 AC XY: 1740 AN XY: 74496

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.00954

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0111 Hom.: 11

Bravo AF: 0.0174

Asia WGS AF: 0.189 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

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	-0.91
Cadd	Benign	0.88
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs2306197; hg19: chr19-39212400; COSMIC: COSV53149186; COSMIC: COSV53149186;