rs509360

Variant names:

• chr11-61781087-A-G
• rs509360
• NM_001127392.3:c.2572+42A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.2572+42A>G		intron_variant	Intron 20 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.2572+42A>G		intron_variant	Intron 20 of 26	1	NM_001127392.3	ENSP00000278836.4

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

GnomAD2 exomes AF: 0.608 AC: 151310 AN: 248854 AF XY: 0.596

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 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 AC: 5202 AN: 33472

Gnomad4 AMR exome AF: 0.825 AC: 36886 AN: 44704

Gnomad4 ASJ exome AF: 0.715 AC: 18675 AN: 26118

Gnomad4 EAS exome AF: 0.467 AC: 18521 AN: 39670

Gnomad4 SAS exome AF: 0.300 AC: 25870 AN: 86250

Gnomad4 FIN exome AF: 0.650 AC: 32791 AN: 50420

Gnomad4 NFE exome AF: 0.676 AC: 751149 AN: 1111784

Gnomad4 Remaining exome AF: 0.627 AC: 37829 AN: 60354

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 AC: 0.175018 AN: 0.175018

Gnomad4 AMR AF: 0.743 AC: 0.742539 AN: 0.742539

Gnomad4 ASJ AF: 0.718 AC: 0.717867 AN: 0.717867

Gnomad4 EAS AF: 0.564 AC: 0.563809 AN: 0.563809

Gnomad4 SAS AF: 0.293 AC: 0.292602 AN: 0.292602

Gnomad4 FIN AF: 0.638 AC: 0.638316 AN: 0.638316

Gnomad4 NFE AF: 0.668 AC: 0.668487 AN: 0.668487

Gnomad4 OTH AF: 0.604 AC: 0.604167 AN: 0.604167

Alfa AF: 0.628 Hom.: 106546

Bravo AF: 0.523

Asia WGS AF: 0.462 AC: 1608 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	-0.91
CADD	Benign	8.2
DANN	Benign	0.52
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

Publications

LitVar

Other links and lift over

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