11-66550352-G-A

Variant names:

• chr11-66550352-G-A
• rs1791690
• NM_001104.4:c.148-887G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001104.4(ACTN3):​c.148-887G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,952 control chromosomes in the GnomAD database, including 18,335 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 0.48 (18335 hom., cov: 31)
• Consequence: ACTN3 NM_001104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN3	NM_001104.4	c.148-887G>A		intron_variant	Intron 1 of 20	ENST00000513398.2	NP_001095.2
ACTN3	NM_001258371.3	c.277-887G>A		intron_variant	Intron 1 of 20		NP_001245300.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN3	ENST00000513398.2	c.148-887G>A		intron_variant	Intron 1 of 20	1	NM_001104.4	ENSP00000426797.1
ACTN3	ENST00000502692.5	c.277-887G>A		intron_variant	Intron 1 of 20	2		ENSP00000422007.1
ACTN3	ENST00000511191.1	n.148-701G>A		intron_variant	Intron 1 of 4	5		ENSP00000426236.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72614 AN: 151834 Hom.: 18305 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.478 AC: 72692 AN: 151952 Hom.: 18335 Cov.: 31 AF XY: 0.474 AC XY: 35194 AN XY: 74270

African (AFR) AF: 0.635 AC: 26295 AN: 41434

American (AMR) AF: 0.376 AC: 5740 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1868 AN: 5166

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5030 AN: 10550

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29422 AN: 67944

Other (OTH) AF: 0.472 AC: 993 AN: 2104

Alfa AF: 0.453 Hom.: 44585

Bravo AF: 0.479

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.42
PhyloP100		-0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1791690; hg19: chr11-66317823;