chr11-61770486-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2
The NM_001127392.3(MYRF):c.701C>T(p.Ser234Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000998 in 1,565,352 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 11 hom. )
Consequence
MYRF
NM_001127392.3 missense
NM_001127392.3 missense
Scores
9
8
Clinical Significance
Conservation
PhyloP100: 5.31
Genes affected
MYRF (HGNC:1181): (myelin regulatory factor) This gene encodes a transcription factor that is required for central nervous system myelination and may regulate oligodendrocyte differentiation. It is thought to act by increasing the expression of genes that effect myelin production but may also directly promote myelin gene expression. Loss of a similar gene in mouse models results in severe demyelination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYRF
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009031802).
BP6
?
Variant 11-61770486-C-T is Benign according to our data. Variant chr11-61770486-C-T is described in ClinVar as [Benign]. Clinvar id is 3050477.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00131 (199/152248) while in subpopulation SAS AF= 0.00414 (20/4826). AF 95% confidence interval is 0.00275. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 199 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYRF | NM_001127392.3 | c.701C>T | p.Ser234Phe | missense_variant | 5/27 | ENST00000278836.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYRF | ENST00000278836.10 | c.701C>T | p.Ser234Phe | missense_variant | 5/27 | 1 | NM_001127392.3 | P2 | |
MYRF | ENST00000265460.9 | c.674C>T | p.Ser225Phe | missense_variant | 5/26 | 1 | A2 | ||
MYRF | ENST00000675319.1 | c.106-1014C>T | intron_variant | ||||||
TMEM258 | ENST00000535042.1 | n.649-1713G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00131 AC: 199AN: 152134Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00174 AC: 307AN: 176466Hom.: 4 AF XY: 0.00189 AC XY: 179AN XY: 94608
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GnomAD4 exome AF: 0.000965 AC: 1364AN: 1413104Hom.: 11 Cov.: 37 AF XY: 0.00105 AC XY: 734AN XY: 698482
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GnomAD4 genome ? AF: 0.00131 AC: 199AN: 152248Hom.: 1 Cov.: 32 AF XY: 0.00180 AC XY: 134AN XY: 74414
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MYRF-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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