Genetic Variant MYRF:c.3301-592G>T (chr11-61785208-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001127392.3(MYRF):c.3301-592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,956 control chromosomes in the GnomAD database, including 8,189 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 0.29 ( 8144 hom., cov: 32)

Exomes 𝑓: 0.28 ( 45 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.25

Publications

277 publications found

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]

MYRF links:

TMEM258 (HGNC:1164): (transmembrane protein 258) Involved in protein N-linked glycosylation. Located in endoplasmic reticulum. Part of oligosaccharyltransferase I complex. [provided by Alliance of Genome Resources, Apr 2022]

TMEM258 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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.3301-592G>T		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.3181-592G>T		intron	N/A	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYRF	ENST00000278836.10	TSL:1 MANE Select	c.3301-592G>T	intron	N/A	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9	TSL:1	c.3181-592G>T	intron	N/A	ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000539361.1	TSL:1	n.3022G>T	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43893

AN:

151998

Hom.:

8121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0827

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.275

AC:

231

AN:

840

Hom.:

Cov.:

AF XY:

0.256

AC XY:

105

AN XY:

410

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.438

AC:

AN:

130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.0556

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.254

AC:

158

AN:

622

Other (OTH)

AF:

0.289

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.289

AC:

43926

AN:

152116

Hom.:

8144

Cov.:

AF XY:

0.295

AC XY:

21927

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0824

AC:

3423

AN:

41520

American (AMR)

AF:

0.488

AC:

7455

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

983

AN:

3466

East Asian (EAS)

AF:

0.553

AC:

2859

AN:

5168

South Asian (SAS)

AF:

0.196

AC:

945

AN:

4818

European-Finnish (FIN)

AF:

0.421

AC:

4452

AN:

10580

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22778

AN:

67956

Other (OTH)

AF:

0.339

AC:

717

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1447

2895

4342

5790

7237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.317

Hom.:

16841

Bravo

AF:

0.290

Asia WGS

AF:

0.390

AC:

1353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.20

(source)

DANN

Benign

0.28

PhyloP100

-5.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over