rs174536

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127392.3(MYRF):​c.3300+70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,275,984 control chromosomes in the GnomAD database, including 79,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8300 hom., cov: 33)
Exomes 𝑓: 0.34 ( 70884 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.358
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 11-61784455-A-C is Benign according to our data. Variant chr11-61784455-A-C is described in ClinVar as [Benign]. Clinvar id is 1259171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYRFNM_001127392.3 linkuse as main transcriptc.3300+70A>C intron_variant ENST00000278836.10 NP_001120864.1 Q9Y2G1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYRFENST00000278836.10 linkuse as main transcriptc.3300+70A>C intron_variant 1 NM_001127392.3 ENSP00000278836.4 Q9Y2G1-1

Frequencies

GnomAD3 genomes
AF:
0.291
AC:
44312
AN:
152050
Hom.:
8277
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0837
Gnomad AMI
AF:
0.233
Gnomad AMR
AF:
0.489
Gnomad ASJ
AF:
0.287
Gnomad EAS
AF:
0.555
Gnomad SAS
AF:
0.200
Gnomad FIN
AF:
0.420
Gnomad MID
AF:
0.345
Gnomad NFE
AF:
0.339
Gnomad OTH
AF:
0.337
GnomAD4 exome
AF:
0.341
AC:
383582
AN:
1123816
Hom.:
70884
Cov.:
15
AF XY:
0.335
AC XY:
190931
AN XY:
570112
show subpopulations
Gnomad4 AFR exome
AF:
0.0706
Gnomad4 AMR exome
AF:
0.641
Gnomad4 ASJ exome
AF:
0.280
Gnomad4 EAS exome
AF:
0.453
Gnomad4 SAS exome
AF:
0.194
Gnomad4 FIN exome
AF:
0.424
Gnomad4 NFE exome
AF:
0.343
Gnomad4 OTH exome
AF:
0.350
GnomAD4 genome
AF:
0.291
AC:
44344
AN:
152168
Hom.:
8300
Cov.:
33
AF XY:
0.297
AC XY:
22123
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0834
Gnomad4 AMR
AF:
0.490
Gnomad4 ASJ
AF:
0.287
Gnomad4 EAS
AF:
0.555
Gnomad4 SAS
AF:
0.201
Gnomad4 FIN
AF:
0.420
Gnomad4 NFE
AF:
0.339
Gnomad4 OTH
AF:
0.341
Alfa
AF:
0.319
Hom.:
3292
Bravo
AF:
0.292
Asia WGS
AF:
0.394
AC:
1369
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 13, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.93
DANN
Benign
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs174536; hg19: chr11-61551927; COSMIC: COSV53892891; COSMIC: COSV53892891; API