rs108499

Variant names:

• chr11-61779765-C-T
• rs108499
• NM_001127392.3:c.2248-77C>T

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.775
• Publications: 63 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=-0.82).
• BP6: Variant 11-61779765-C-T is Benign according to our data. Variant chr11-61779765-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.2248-77C>T		intron_variant	Intron 16 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.2248-77C>T		intron_variant	Intron 16 of 26	1	NM_001127392.3	ENSP00000278836.4

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

African (AFR) AF: 0.0575 AC: 1689 AN: 29378

American (AMR) AF: 0.642 AC: 24354 AN: 37914

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5519 AN: 23298

East Asian (EAS) AF: 0.452 AC: 16538 AN: 36624

South Asian (SAS) AF: 0.156 AC: 11960 AN: 76668

European-Finnish (FIN) AF: 0.349 AC: 17723 AN: 50710

Middle Eastern (MID) AF: 0.225 AC: 1205 AN: 5346

European-Non Finnish (NFE) AF: 0.334 AC: 317621 AN: 950650

Other (OTH) AF: 0.333 AC: 17653 AN: 53090

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

African (AFR) AF: 0.0747 AC: 3103 AN: 41512

American (AMR) AF: 0.482 AC: 7375 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2839 AN: 5168

South Asian (SAS) AF: 0.162 AC: 780 AN: 4818

European-Finnish (FIN) AF: 0.341 AC: 3610 AN: 10592

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22088 AN: 67978

Other (OTH) AF: 0.335 AC: 708 AN: 2112

Alfa AF: 0.320 Hom.: 24023

Bravo AF: 0.283

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.30
PhyloP100		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs108499; hg19: chr11-61547237; COSMIC: COSV53888941; COSMIC: COSV53888941;