rs198475

Positions:

• chr11-61758599-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127392.3(MYRF):​c.46+5809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,120 control chromosomes in the GnomAD database, including 38,632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (38632 hom., cov: 34)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.46+5809T>C		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.46+5809T>C		intron_variant		1	NM_001127392.3	P2
MYRF	ENST00000265460.9	c.19+3157T>C		intron_variant		1		A2
MYRF	ENST00000537766.1	n.149+5809T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106840 AN: 152002 Hom.: 38615 Cov.: 34

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.690

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.703 AC: 106890 AN: 152120 Hom.: 38632 Cov.: 34 AF XY: 0.711 AC XY: 52861 AN XY: 74376

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.691

Alfa AF: 0.743 Hom.: 67208

Bravo AF: 0.689

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs198475; hg19: chr11-61526071; COSMIC: COSV53887208; COSMIC: COSV53887208;