rs509556

Positions:

• chr11-66558891-A-G
• chr11-66558891-A-T

Variant summary

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

The NM_001104.4(ACTN3):​c.1277-345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 247,114 control chromosomes in the GnomAD database, including 44,593 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 0.61 (30027 hom., cov: 32)
  • Exomes 𝑓: 0.55 (14566 hom.)
• Consequence: ACTN3 NM_001104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

ACTN3 (HGNC:165): (actinin alpha 3) This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Feb 2014]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN3	NM_001104.4	c.1277-345A>G		intron_variant		ENST00000513398.2
ACTN3	NM_001258371.3	c.1406-345A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN3	ENST00000513398.2	c.1277-345A>G		intron_variant		1	NM_001104.4	P1
	ENST00000504911.1	n.555T>C		non_coding_transcript_exon_variant	2/2	3
ACTN3	ENST00000502692.5	c.1406-345A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92891 AN: 151974 Hom.: 29968 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.546 AC: 51836 AN: 95022 Hom.: 14566 Cov.: 0 AF XY: 0.541 AC XY: 25905 AN XY: 47922

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.611 AC: 92999 AN: 152092 Hom.: 30027 Cov.: 32 AF XY: 0.607 AC XY: 45134 AN XY: 74348

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.576

Alfa AF: 0.546 Hom.: 8121

Bravo AF: 0.609

Asia WGS AF: 0.494 AC: 1719 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	1.0
DANN	Benign	0.37

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: rs509556; hg19: chr11-66326362;