11-61785208-G-T

Position:

• chr11-61785208-G-T

Variant summary

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

The ENST00000278836.10(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 ENST00000278836.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.25

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]

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.3301-592G>T		intron_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.3301-592G>T		intron_variant		1	NM_001127392.3	ENSP00000278836	P2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43893 AN: 151998 Hom.: 8121 Cov.: 32

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.: 45 Cov.: 0 AF XY: 0.256 AC XY: 105 AN XY: 410

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.289 AC: 43926 AN: 152116 Hom.: 8144 Cov.: 32 AF XY: 0.295 AC XY: 21927 AN XY: 74364

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.339

Alfa AF: 0.311 Hom.: 3822

Bravo AF: 0.290

Asia WGS AF: 0.390 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.28

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: rs174537; hg19: chr11-61552680;