rs174528

chr11-61776027-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001127392.3(MYRF):c.1312-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,610,424 control chromosomes in the GnomAD database, including 125,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14121 hom., cov: 32)
  • Exomes 𝑓: 0.38 (111727 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.109

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-61776027-T-C is Benign according to our data. Variant chr11-61776027-T-C is described in ClinVar as [Benign]. Clinvar id is 1225263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.1312-29T>C		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.1312-29T>C		intron_variant		1	NM_001127392.3	P2
MYRF	ENST00000265460.9	c.1285-29T>C		intron_variant		1		A2
MYRF	ENST00000675319.1	c.677-29T>C		intron_variant
TMEM258	ENST00000535042.1	n.480-1880A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63672 AN: 151660 Hom.: 14065 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.441

GnomAD3 exomes AF: 0.419 AC: 104830 AN: 250070 Hom.: 25203 AF XY: 0.397 AC XY: 53627 AN XY: 135212

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.569

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.382 AC: 557001 AN: 1458646 Hom.: 111727 Cov.: 32 AF XY: 0.374 AC XY: 271611 AN XY: 725862

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.420 AC: 63787 AN: 151778 Hom.: 14121 Cov.: 32 AF XY: 0.421 AC XY: 31240 AN XY: 74172

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.443

Alfa AF: 0.408 Hom.: 5107

Bravo AF: 0.437

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.81
Cadd	Benign	1.6
Dann	Benign	0.60

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: rs174528; hg19: chr11-61543499; COSMIC: COSV53888927; COSMIC: COSV53888927;