chr11-61776027-T-C

Variant names:

• chr11-61776027-T-C
• rs174528
• NM_001127392.3:c.1312-29T>C

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.1312-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,610,424 control chromosomes in the GnomAD database, including 125,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.42 (14121 hom., cov: 32)
  • Exomes 𝑓: 0.38 (111727 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.109
• Publications: 74 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-61776027-T-C is Benign according to our data. Variant chr11-61776027-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.1312-29T>C		intron_variant	Intron 8 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.1312-29T>C		intron_variant	Intron 8 of 26	1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000265460.9	c.1285-29T>C		intron_variant	Intron 8 of 25	1		ENSP00000265460.5
MYRF	ENST00000675319.1	c.676-29T>C		intron_variant	Intron 4 of 22			ENSP00000502795.1
TMEM258	ENST00000535042.1	n.480-1880A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63672 AN: 151660 Hom.: 14065 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.441

GnomAD2 exomes AF: 0.419 AC: 104830 AN: 250070 AF XY: 0.397

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.569

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.382 AC: 557001 AN: 1458646 Hom.: 111727 Cov.: 32 AF XY: 0.374 AC XY: 271611 AN XY: 725862

African (AFR) AF: 0.461 AC: 15396 AN: 33420

American (AMR) AF: 0.699 AC: 31219 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8226 AN: 26084

East Asian (EAS) AF: 0.466 AC: 18473 AN: 39664

South Asian (SAS) AF: 0.201 AC: 17328 AN: 86208

European-Finnish (FIN) AF: 0.429 AC: 22862 AN: 53256

Middle Eastern (MID) AF: 0.310 AC: 1784 AN: 5764

European-Non Finnish (NFE) AF: 0.376 AC: 417317 AN: 1109310

Other (OTH) AF: 0.405 AC: 24396 AN: 60270

GnomAD4 genome AF: 0.420 AC: 63787 AN: 151778 Hom.: 14121 Cov.: 32 AF XY: 0.421 AC XY: 31240 AN XY: 74172

African (AFR) AF: 0.466 AC: 19268 AN: 41328

American (AMR) AF: 0.561 AC: 8566 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2886 AN: 5144

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4822

European-Finnish (FIN) AF: 0.426 AC: 4497 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25158 AN: 67872

Other (OTH) AF: 0.443 AC: 934 AN: 2106

Alfa AF: 0.399 Hom.: 23942

Bravo AF: 0.437

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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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	-0.81
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.11
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs174528; hg19: chr11-61543499; COSMIC: COSV53888927; COSMIC: COSV53888927;