chr11-61770057-T-G

Position:

• chr11-61770057-T-G

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.461-189T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,782 control chromosomes in the GnomAD database, including 2,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2971 hom., cov: 32)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55

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=-0.84).
• BP6: Variant 11-61770057-T-G is Benign according to our data. Variant chr11-61770057-T-G is described in ClinVar as [Benign]. Clinvar id is 1230861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.461-189T>G		intron_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.461-189T>G		intron_variant		1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000265460.9	c.434-189T>G		intron_variant		1		ENSP00000265460.5
MYRF	ENST00000675319.1	c.105-1443T>G		intron_variant				ENSP00000502795.1
TMEM258	ENST00000535042.1	n.649-1284A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27548 AN: 151664 Hom.: 2973 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27546 AN: 151782 Hom.: 2971 Cov.: 32 AF XY: 0.178 AC XY: 13235 AN XY: 74194

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.232

Alfa AF: 0.179 Hom.: 353

Bravo AF: 0.190

Asia WGS AF: 0.277 AC: 962 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	-0.84
CADD	Benign	0.47
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2269928; hg19: chr11-61537529;