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
• Publications: 65 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=-0.91).
• BP6: Variant 11-61781087-A-G is Benign according to our data. Variant chr11-61781087-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127392.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	NM_001127392.3	MANE Select	c.2572+42A>G		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.2467+42A>G		intron	N/A	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.2572+42A>G		intron	N/A	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.2467+42A>G		intron	N/A	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.2575+42A>G		intron	N/A	ENSP00000526870.1

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

African (AFR) AF: 0.155 AC: 5202 AN: 33472

American (AMR) AF: 0.825 AC: 36886 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 18675 AN: 26118

East Asian (EAS) AF: 0.467 AC: 18521 AN: 39670

South Asian (SAS) AF: 0.300 AC: 25870 AN: 86250

European-Finnish (FIN) AF: 0.650 AC: 32791 AN: 50420

Middle Eastern (MID) AF: 0.652 AC: 3756 AN: 5764

European-Non Finnish (NFE) AF: 0.676 AC: 751149 AN: 1111784

Other (OTH) 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

African (AFR) AF: 0.175 AC: 7244 AN: 41390

American (AMR) AF: 0.743 AC: 11346 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2491 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2907 AN: 5156

South Asian (SAS) AF: 0.293 AC: 1408 AN: 4812

European-Finnish (FIN) AF: 0.638 AC: 6747 AN: 10570

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45425 AN: 67952

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.628 Hom.: 106546

Bravo AF: 0.523

Asia WGS AF: 0.462 AC: 1608 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.52
PhyloP100		1.1
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: rs509360; hg19: chr11-61548559; COSMIC: COSV53888948; COSMIC: COSV53888948;