11-61758599-T-C

Variant names:

• chr11-61758599-T-C
• rs198475
• NM_001127392.3:c.46+5809T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

MYRF Gene-Disease associations (from GenCC):

• cardiac-urogenital syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• encephalitis/encephalopathy, mild, with reversible myelin vacuolization

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127392.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	NM_001127392.3	MANE Select	c.46+5809T>C		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.19+3157T>C		intron	N/A	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.46+5809T>C		intron	N/A	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.19+3157T>C		intron	N/A	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.46+5809T>C		intron	N/A	ENSP00000526870.1

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

African (AFR) AF: 0.533 AC: 22089 AN: 41452

American (AMR) AF: 0.757 AC: 11581 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3962 AN: 5170

South Asian (SAS) AF: 0.755 AC: 3645 AN: 4828

European-Finnish (FIN) AF: 0.882 AC: 9361 AN: 10616

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51456 AN: 67978

Other (OTH) AF: 0.691 AC: 1459 AN: 2110

Alfa AF: 0.732 Hom.: 114892

Bravo AF: 0.689

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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