rs77247855
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000255078.8(IGHMBP2):c.1757-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,522 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0074 ( 13 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 12 hom. )
Consequence
IGHMBP2
ENST00000255078.8 intron
ENST00000255078.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.31
Genes affected
IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 11-68936219-C-A is Benign according to our data. Variant chr11-68936219-C-A is described in ClinVar as [Benign]. Clinvar id is 258561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00737 (1123/152318) while in subpopulation AFR AF= 0.0262 (1088/41574). AF 95% confidence interval is 0.0249. There are 13 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.1757-18C>A | intron_variant | ENST00000255078.8 | NP_002171.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.1757-18C>A | intron_variant | 1 | NM_002180.3 | ENSP00000255078 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00735 AC: 1118AN: 152200Hom.: 13 Cov.: 33
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GnomAD3 exomes AF: 0.00201 AC: 502AN: 249630Hom.: 7 AF XY: 0.00148 AC XY: 200AN XY: 135142
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GnomAD4 exome AF: 0.000686 AC: 1002AN: 1461204Hom.: 12 Cov.: 31 AF XY: 0.000604 AC XY: 439AN XY: 726926
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GnomAD4 genome AF: 0.00737 AC: 1123AN: 152318Hom.: 13 Cov.: 33 AF XY: 0.00706 AC XY: 526AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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