rs174534

Positions:

• chr11-61781986-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127392.3(MYRF):​c.3016+162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 807,536 control chromosomes in the GnomAD database, including 49,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (8100 hom., cov: 34)
  • Exomes 𝑓: 0.34 (40992 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-61781986-A-G is Benign according to our data. Variant chr11-61781986-A-G is described in ClinVar as [Benign]. Clinvar id is 1227305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.3016+162A>G		intron_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.3016+162A>G		intron_variant		1	NM_001127392.3	ENSP00000278836	P2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43386 AN: 152134 Hom.: 8077 Cov.: 34

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.341 AC: 223645 AN: 655284 Hom.: 40992 Cov.: 9 AF XY: 0.336 AC XY: 110561 AN XY: 328606

Gnomad4 AFR exome AF: 0.0652

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.285 AC: 43418 AN: 152252 Hom.: 8100 Cov.: 34 AF XY: 0.287 AC XY: 21368 AN XY: 74448

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.346

Alfa AF: 0.323 Hom.: 5139

Bravo AF: 0.294

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.038
DANN	Benign	0.36

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: rs174534; hg19: chr11-61549458;