rs138139611
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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.2400C>T(p.Asp800=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000435 in 1,612,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00067 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00041 ( 1 hom. )
Consequence
ACTN4
NM_004924.6 synonymous
NM_004924.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.29
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=-0.36).
BP6
Variant 19-38728008-C-T is Benign according to our data. Variant chr19-38728008-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 585361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00067 (102/152138) while in subpopulation EAS AF= 0.00504 (26/5156). AF 95% confidence interval is 0.00353. There are 0 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 102 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTN4 | NM_004924.6 | c.2400C>T | p.Asp800= | synonymous_variant | 19/21 | ENST00000252699.7 | NP_004915.2 | |
LOC107985291 | XR_001753937.2 | n.169+180G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTN4 | ENST00000252699.7 | c.2400C>T | p.Asp800= | synonymous_variant | 19/21 | 1 | NM_004924.6 | ENSP00000252699 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000678 AC: 103AN: 152020Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00115 AC: 285AN: 248420Hom.: 1 AF XY: 0.00110 AC XY: 149AN XY: 134920
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GnomAD4 exome AF: 0.000411 AC: 600AN: 1460806Hom.: 1 Cov.: 32 AF XY: 0.000424 AC XY: 308AN XY: 726676
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GnomAD4 genome AF: 0.000670 AC: 102AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.000834 AC XY: 62AN XY: 74376
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 27, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2023 | - - |
Focal segmental glomerulosclerosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 01, 2020 | - - |
Focal segmental glomerulosclerosis 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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