rs140707871
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004924.6(ACTN4):c.1770C>T(p.Ile590=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,613,998 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 3 hom. )
Consequence
ACTN4
NM_004924.6 synonymous
NM_004924.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
ACTN4 (HGNC:166): (actinin alpha 4) 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 nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
Variant 19-38724234-C-T is Benign according to our data. Variant chr19-38724234-C-T is described in ClinVar as [Benign]. Clinvar id is 259570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00217 (331/152340) while in subpopulation AFR AF= 0.00763 (317/41570). AF 95% confidence interval is 0.00693. There are 1 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 331 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN4 | NM_004924.6 | c.1770C>T | p.Ile590= | synonymous_variant | 15/21 | ENST00000252699.7 | |
LOC107985291 | XR_001753937.2 | n.169+3954G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN4 | ENST00000252699.7 | c.1770C>T | p.Ile590= | synonymous_variant | 15/21 | 1 | NM_004924.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00218 AC: 332AN: 152222Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000709 AC: 178AN: 251082Hom.: 2 AF XY: 0.000508 AC XY: 69AN XY: 135796
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GnomAD4 exome AF: 0.000232 AC: 339AN: 1461658Hom.: 3 Cov.: 37 AF XY: 0.000197 AC XY: 143AN XY: 727144
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GnomAD4 genome ? AF: 0.00217 AC: 331AN: 152340Hom.: 1 Cov.: 32 AF XY: 0.00242 AC XY: 180AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 05, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 19, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Focal segmental glomerulosclerosis 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 01, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at