1-229431440-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001100.4(ACTA1):c.*58_*59insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,608,512 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (11 hom.)
• Consequence: ACTA1 NM_001100.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.847

Genes affected

ACTA1 (HGNC:129): (actin alpha 1, skeletal muscle) The product encoded by this gene belongs to the actin family of proteins, which are highly conserved proteins that play a role in cell motility, structure and integrity. Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. This actin is an alpha actin that is found in skeletal muscle. Mutations in this gene cause a variety of myopathies, including nemaline myopathy, congenital myopathy with excess of thin myofilaments, congenital myopathy with cores, and congenital myopathy with fiber-type disproportion, diseases that lead to muscle fiber defects with manifestations such as hypotonia. [provided by RefSeq, Sep 2019]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-229431440-G-GC is Benign according to our data. Variant chr1-229431440-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 1207757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00594 (904/152136) while in subpopulation AFR AF= 0.0206 (856/41506). AF 95% confidence interval is 0.0195. There are 7 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTA1	NM_001100.4	c.*58_*59insG		3_prime_UTR_variant	7/7	ENST00000366684.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTA1	ENST00000366684.7	c.*58_*59insG		3_prime_UTR_variant	7/7	1	NM_001100.4	P1
	ENST00000702606.1	n.82dup		non_coding_transcript_exon_variant	1/1
ACTA1	ENST00000366683.4	c.*58_*59insG		3_prime_UTR_variant	7/7	5
ACTA1	ENST00000684723.1	c.*58_*59insG		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 898 AN: 152018 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000654 AC: 953 AN: 1456376 Hom.: 11 Cov.: 30 AF XY: 0.000534 AC XY: 387 AN XY: 724638

Gnomad4 AFR exome AF: 0.0227

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000289

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00594 AC: 904 AN: 152136 Hom.: 7 Cov.: 32 AF XY: 0.00570 AC XY: 424 AN XY: 74360

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00236

Bravo AF: 0.00651

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs148828901; hg19: chr1-229567187;