rs509360

chr11-61781087-A-G

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.2572+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,610,482 control chromosomes in the GnomAD database, including 334,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (24932 hom., cov: 32)
  • Exomes 𝑓: 0.64 (309699 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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=-0.91).
• BP6: Variant 11-61781087-A-G is Benign according to our data. Variant chr11-61781087-A-G is described in ClinVar as [Benign]. Clinvar id is 1272274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.2572+42A>G		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.2572+42A>G		intron_variant		1	NM_001127392.3	P2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79640 AN: 151828 Hom.: 24916 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.604

GnomAD3 exomes AF: 0.608 AC: 151310 AN: 248854 Hom.: 50782 AF XY: 0.596 AC XY: 80259 AN XY: 134700

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.834

Gnomad ASJ exome AF: 0.709

Gnomad EAS exome AF: 0.571

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.645

Gnomad NFE exome AF: 0.674

Gnomad OTH exome AF: 0.663

GnomAD4 exome AF: 0.638 AC: 930679 AN: 1458536 Hom.: 309699 Cov.: 48 AF XY: 0.628 AC XY: 455550 AN XY: 725740

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.524 AC: 79671 AN: 151946 Hom.: 24932 Cov.: 32 AF XY: 0.524 AC XY: 38909 AN XY: 74288

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.604

Alfa AF: 0.650 Hom.: 49318

Bravo AF: 0.523

Asia WGS AF: 0.462 AC: 1608 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	8.2
Dann	Benign	0.52

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: rs509360; hg19: chr11-61548559; COSMIC: COSV53888948; COSMIC: COSV53888948;