rs108499

Positions:

• chr11-61779765-C-T

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.2248-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,415,824 control chromosomes in the GnomAD database, including 81,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7527 hom., cov: 33)
  • Exomes 𝑓: 0.33 (73991 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.775

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=-0.82).
• BP6: Variant 11-61779765-C-T is Benign according to our data. Variant chr11-61779765-C-T is described in ClinVar as [Benign]. Clinvar id is 1236921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.2248-77C>T		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.2248-77C>T		intron_variant		1	NM_001127392.3	P2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41597 AN: 152028 Hom.: 7504 Cov.: 33

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.328 AC: 414262 AN: 1263678 Hom.: 73991 Cov.: 17 AF XY: 0.321 AC XY: 201626 AN XY: 627816

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.642

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.274 AC: 41631 AN: 152146 Hom.: 7527 Cov.: 33 AF XY: 0.276 AC XY: 20519 AN XY: 74374

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.335

Alfa AF: 0.319 Hom.: 9113

Bravo AF: 0.283

Asia WGS AF: 0.352 AC: 1222 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	-0.82
CADD	Benign	13
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs108499; hg19: chr11-61547237; COSMIC: COSV53888941; COSMIC: COSV53888941;