chr1-39084245-C-CAGTGAGCGGTCATGTCGG
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The ENST00000567887.5(MACF1):c.39_56dup(p.Cys20_Ser25dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000604 in 152,292 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 2 hom. )
Failed GnomAD Quality Control
Consequence
MACF1
ENST00000567887.5 inframe_insertion
ENST00000567887.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.44
Genes affected
MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in ENST00000567887.5.
BP6
?
Variant 1-39084245-C-CAGTGAGCGGTCATGTCGG is Benign according to our data. Variant chr1-39084245-C-CAGTGAGCGGTCATGTCGG is described in ClinVar as [Likely_benign]. Clinvar id is 2848268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000604 (92/152292) while in subpopulation SAS AF= 0.00207 (10/4828). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 92 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MACF1 | NM_012090.5 | c.39_56dup | p.Cys20_Ser25dup | inframe_insertion | 1/93 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MACF1 | ENST00000361689.7 | c.39_56dup | p.Cys20_Ser25dup | inframe_insertion | 2/94 | 5 | |||
MACF1 | ENST00000372915.8 | c.39_56dup | p.Cys20_Ser25dup | inframe_insertion | 1/96 | 5 | P1 | ||
MACF1 | ENST00000484793.5 | c.39_56dup | p.Cys20_Ser25dup | inframe_insertion | 3/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000605 AC: 92AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000438 AC: 110AN: 250904Hom.: 0 AF XY: 0.000428 AC XY: 58AN XY: 135670
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000350 AC: 511AN: 1460924Hom.: 2 Cov.: 30 AF XY: 0.000377 AC XY: 274AN XY: 726814
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.000604 AC: 92AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 24, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2023 | - - |
MACF1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 26, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at