rs509556

Variant names:

• chr11-66558891-A-G
• rs509556
• NM_001104.4:c.1277-345A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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:58248):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN3	NM_001104.4	MANE Select	c.1277-345A>G		intron	N/A	NP_001095.2
	ACTN3	NM_001258371.3		c.1406-345A>G		intron	N/A	NP_001245300.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN3	ENST00000513398.2	TSL:1 MANE Select	c.1277-345A>G		intron	N/A	ENSP00000426797.1
	ENSG00000250105	ENST00000504911.1	TSL:3	n.555T>C		non_coding_transcript_exon	Exon 2 of 2
	ACTN3	ENST00000502692.5	TSL:2	c.1406-345A>G		intron	N/A	ENSP00000422007.1

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

African (AFR) AF: 0.827 AC: 2871 AN: 3470

American (AMR) AF: 0.391 AC: 1098 AN: 2810

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 2159 AN: 4076

East Asian (EAS) AF: 0.483 AC: 3819 AN: 7912

South Asian (SAS) AF: 0.357 AC: 340 AN: 952

European-Finnish (FIN) AF: 0.625 AC: 3680 AN: 5886

Middle Eastern (MID) AF: 0.550 AC: 288 AN: 524

European-Non Finnish (NFE) AF: 0.542 AC: 33918 AN: 62622

Other (OTH) AF: 0.541 AC: 3663 AN: 6770

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

African (AFR) AF: 0.833 AC: 34566 AN: 41514

American (AMR) AF: 0.447 AC: 6825 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1830 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2759 AN: 5166

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4822

European-Finnish (FIN) AF: 0.634 AC: 6697 AN: 10556

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36659 AN: 67966

Other (OTH) AF: 0.576 AC: 1218 AN: 2114

Alfa AF: 0.558 Hom.: 14467

Bravo AF: 0.609

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs509556; hg19: chr11-66326362;