1-229431173-C-CT

Position:

• chr1-229431173-C-CT

Variant summary

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

The ENST00000684723.1(ACTA1):​c.*325_*326insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 400,268 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (7 hom.)
• Consequence: ACTA1 ENST00000684723.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-229431173-C-CT is Benign according to our data. Variant chr1-229431173-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1212858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0039 (594/152332) while in subpopulation NFE AF= 0.00353 (240/68024). AF 95% confidence interval is 0.00316. There are 7 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTA1	ENST00000684723.1	c.*325_*326insA		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152214 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00313 AC: 777 AN: 247936 Hom.: 7 AF XY: 0.00292 AC XY: 391 AN XY: 133690

Gnomad4 AFR exome AF: 0.000850

Gnomad4 AMR exome AF: 0.00155

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000868

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.00330

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152332 Hom.: 7 Cov.: 32 AF XY: 0.00427 AC XY: 318 AN XY: 74500

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.00353

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00325

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

Apr 10, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs531419880; hg19: chr1-229566920;