rs174532

chr11-61781402-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.2764+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,571,074 control chromosomes in the GnomAD database, including 58,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (4099 hom., cov: 33)
  • Exomes 𝑓: 0.26 (54005 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.590

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 11-61781402-G-A is Benign according to our data. Variant chr11-61781402-G-A is described in ClinVar as [Benign]. Clinvar id is 1257534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.2764+73G>A		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.2764+73G>A		intron_variant		1	NM_001127392.3	P2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30325 AN: 152108 Hom.: 4099 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.261 AC: 370919 AN: 1418848 Hom.: 54005 Cov.: 31 AF XY: 0.256 AC XY: 179717 AN XY: 702446

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.000459

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.199 AC: 30317 AN: 152226 Hom.: 4099 Cov.: 33 AF XY: 0.194 AC XY: 14419 AN XY: 74414

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.224

Alfa AF: 0.285 Hom.: 8833

Bravo AF: 0.195

Asia WGS AF: 0.0400 AC: 143 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	-0.82
Cadd	Benign	13
Dann	Benign	0.62

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: rs174532; hg19: chr11-61548874;