chr11-66559110-T-C

Position:

• chr11-66559110-T-C

Variant summary

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

The NM_001104.4(ACTN3):​c.1277-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,045,904 control chromosomes in the GnomAD database, including 19,047 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 0.20 (3342 hom., cov: 32)
  • Exomes 𝑓: 0.18 (15705 hom.)
• Consequence: ACTN3 NM_001104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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]

ENSG00000250105 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN3	NM_001104.4	c.1277-126T>C		intron_variant		ENST00000513398.2	NP_001095.2
ACTN3	NM_001258371.3	c.1406-126T>C		intron_variant			NP_001245300.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN3	ENST00000513398.2	c.1277-126T>C		intron_variant		1	NM_001104.4	ENSP00000426797.1
ACTN3	ENST00000502692.5	c.1406-126T>C		intron_variant		2		ENSP00000422007.1
ENSG00000250105	ENST00000504911.1	n.336A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30643 AN: 151864 Hom.: 3340 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.184 AC: 164545 AN: 893922 Hom.: 15705 Cov.: 12 AF XY: 0.184 AC XY: 80194 AN XY: 436394

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.202 AC: 30667 AN: 151982 Hom.: 3342 Cov.: 32 AF XY: 0.201 AC XY: 14959 AN XY: 74288

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.170

Alfa AF: 0.171 Hom.: 4646

Bravo AF: 0.197

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.39

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: rs2275998; hg19: chr11-66326581; COSMIC: COSV59749410; COSMIC: COSV59749410;