chr1-236686571-GCGCCCGC-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_001103.4(ACTN2):c.-84_-78del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,312,918 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.011 ( 25 hom., cov: 30)
Exomes 𝑓: 0.0021 ( 38 hom. )
Consequence
ACTN2
NM_001103.4 5_prime_UTR
NM_001103.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.94
Genes affected
ACTN2 (HGNC:164): (actinin alpha 2) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 1-236686571-GCGCCCGC-G is Benign according to our data. Variant chr1-236686571-GCGCCCGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 296493.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1679/150916) while in subpopulation AFR AF= 0.0361 (1486/41214). AF 95% confidence interval is 0.0345. There are 25 homozygotes in gnomad4. There are 804 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1671 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.-84_-78del | 5_prime_UTR_variant | 1/21 | ENST00000366578.6 | ||
ACTN2 | NM_001278343.2 | c.-84_-78del | 5_prime_UTR_variant | 1/21 | |||
ACTN2 | NR_184402.1 | n.92_98del | non_coding_transcript_exon_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN2 | ENST00000366578.6 | c.-84_-78del | 5_prime_UTR_variant | 1/21 | 1 | NM_001103.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0111 AC: 1671AN: 150818Hom.: 25 Cov.: 30
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GnomAD4 exome AF: 0.00214 AC: 2483AN: 1162002Hom.: 38 AF XY: 0.00205 AC XY: 1162AN XY: 567226
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GnomAD4 genome ? AF: 0.0111 AC: 1679AN: 150916Hom.: 25 Cov.: 30 AF XY: 0.0109 AC XY: 804AN XY: 73762
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at