rs7248577

Positions:

• chr19-38718155-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.1291+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,550,290 control chromosomes in the GnomAD database, including 3,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (280 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3352 hom.)
• Consequence: ACTN4 NM_004924.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.572

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=-0.79).
• BP6: Variant 19-38718155-C-T is Benign according to our data. Variant chr19-38718155-C-T is described in ClinVar as [Benign]. Clinvar id is 1237308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN4	NM_004924.6	c.1291+81C>T		intron_variant		ENST00000252699.7
LOC107985291	XR_001753937.2	n.169+10033G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN4	ENST00000252699.7	c.1291+81C>T		intron_variant		1	NM_004924.6	A1

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9098 AN: 152132 Hom.: 280 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0960

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0659 AC: 92165 AN: 1398040 Hom.: 3352 Cov.: 31 AF XY: 0.0669 AC XY: 46157 AN XY: 690050

Gnomad4 AFR exome AF: 0.0645

Gnomad4 AMR exome AF: 0.0733

Gnomad4 ASJ exome AF: 0.0620

Gnomad4 EAS exome AF: 0.0465

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.0656

Gnomad4 OTH exome AF: 0.0664

GnomAD4 genome AF: 0.0598 AC: 9107 AN: 152250 Hom.: 280 Cov.: 32 AF XY: 0.0588 AC XY: 4380 AN XY: 74442

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0462

Gnomad4 SAS AF: 0.0954

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0560 Hom.: 29

Bravo AF: 0.0631

Asia WGS AF: 0.0900 AC: 312 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 09, 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	-0.79
CADD	Benign	1.3
DANN	Benign	0.83

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: rs7248577; hg19: chr19-39208795;