NM_001127392.3:c.47-1106A>G

Variant names:

• chr11-61764519-A-G
• rs55903902
• NM_001127392.3:c.47-1106A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127392.3(MYRF):​c.47-1106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,088 control chromosomes in the GnomAD database, including 3,307 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 0.19 (3307 hom., cov: 33)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 5 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.47-1106A>G		intron_variant	Intron 1 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.47-1106A>G		intron_variant	Intron 1 of 26	1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000265460.9	c.20-1106A>G		intron_variant	Intron 1 of 25	1		ENSP00000265460.5
MYRF	ENST00000537766.1	n.150-1106A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29617 AN: 151970 Hom.: 3309 Cov.: 33

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.195 AC: 29616 AN: 152088 Hom.: 3307 Cov.: 33 AF XY: 0.190 AC XY: 14147 AN XY: 74358

African (AFR) AF: 0.0985 AC: 4088 AN: 41516

American (AMR) AF: 0.289 AC: 4410 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3466

East Asian (EAS) AF: 0.285 AC: 1467 AN: 5154

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10594

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15564 AN: 67936

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.208 Hom.: 633

Bravo AF: 0.203

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.5
DANN	Benign	0.92
PhyloP100		0.017
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: rs55903902; hg19: chr11-61531991;