rs174534

Variant names:

• chr11-61781986-A-G
• rs174534
• ENST00000539361.1:n.50A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000539361.1(MYRF):​n.50A>G variant causes a non coding transcript exon 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 ENST00000539361.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 68 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]

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.3016+162A>G		intron_variant	Intron 22 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.3016+162A>G		intron_variant	Intron 22 of 26	1	NM_001127392.3	ENSP00000278836.4

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

African (AFR) AF: 0.0652 AC: 1057 AN: 16202

American (AMR) AF: 0.596 AC: 9135 AN: 15336

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3714 AN: 14278

East Asian (EAS) AF: 0.442 AC: 13399 AN: 30328

South Asian (SAS) AF: 0.178 AC: 6569 AN: 37008

European-Finnish (FIN) AF: 0.363 AC: 10239 AN: 28244

Middle Eastern (MID) AF: 0.239 AC: 563 AN: 2354

European-Non Finnish (NFE) AF: 0.350 AC: 167599 AN: 479284

Other (OTH) AF: 0.353 AC: 11370 AN: 32250

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

African (AFR) AF: 0.0774 AC: 3219 AN: 41580

American (AMR) AF: 0.499 AC: 7631 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2867 AN: 5176

South Asian (SAS) AF: 0.175 AC: 847 AN: 4832

European-Finnish (FIN) AF: 0.349 AC: 3698 AN: 10604

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23213 AN: 67984

Other (OTH) AF: 0.346 AC: 732 AN: 2114

Alfa AF: 0.325 Hom.: 19168

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.038
DANN	Benign	0.36
PhyloP100		-1.5
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: rs174534; hg19: chr11-61549458;