rs707216

Positions:

• chr1-236702268-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001103.4(ACTN2):​c.126+15469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,102 control chromosomes in the GnomAD database, including 1,783 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 0.15 (1783 hom., cov: 32)
• Consequence: ACTN2 NM_001103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

Genes affected

ACTN2 (HGNC:164): (actinin alpha 2) 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 muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN2	NM_001103.4	c.126+15469G>A		intron_variant		ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2	c.126+15469G>A		intron_variant			NP_001265272.1
ACTN2	NR_184402.1	n.301+15469G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000366578.6	c.126+15469G>A		intron_variant		1	NM_001103.4	ENSP00000355537	A1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22995 AN: 151984 Hom.: 1772 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.151 AC: 23041 AN: 152102 Hom.: 1783 Cov.: 32 AF XY: 0.152 AC XY: 11285 AN XY: 74358

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.139

Alfa AF: 0.157 Hom.: 2536

Bravo AF: 0.148

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.68

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: rs707216; hg19: chr1-236865568;