11-61770218-G-A

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.461-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,562,578 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (70 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (426 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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 11-61770218-G-A is Benign according to our data. Variant chr11-61770218-G-A is described in ClinVar as [Benign]. Clinvar id is 1275657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.461-28G>A		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.461-28G>A		intron_variant		1	NM_001127392.3	P2
MYRF	ENST00000265460.9	c.434-28G>A		intron_variant		1		A2
MYRF	ENST00000675319.1	c.106-1282G>A		intron_variant
TMEM258	ENST00000535042.1	n.649-1445C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00862 AC: 1310 AN: 151964 Hom.: 70 Cov.: 31

Gnomad AFR AF: 0.00177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00959

GnomAD3 exomes AF: 0.0219 AC: 4285 AN: 195606 Hom.: 312 AF XY: 0.0163 AC XY: 1702 AN XY: 104650

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00110

Gnomad SAS exome AF: 0.0000471

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000699

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.00415 AC: 5848 AN: 1410496 Hom.: 426 Cov.: 33 AF XY: 0.00347 AC XY: 2413 AN XY: 696228

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000678

Gnomad4 SAS exome AF: 0.0000518

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000368

Gnomad4 OTH exome AF: 0.00406

GnomAD4 genome AF: 0.00868 AC: 1320 AN: 152082 Hom.: 70 Cov.: 31 AF XY: 0.00992 AC XY: 737 AN XY: 74328

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00949

Alfa AF: 0.00534 Hom.: 8

Bravo AF: 0.0150

Asia WGS AF: 0.00549 AC: 19 AN: 3476

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 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.7
Dann	Benign	0.73

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: rs182542962; hg19: chr11-61537690;