Variant rs174528 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.109

Variant links:

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]

MYRF links:

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]

TMEM258 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 5 / 10). 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 id 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/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.1312-29T>C		intron_variant		ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYRF	ENST00000278836.10 link	c.1312-29T>C	intron_variant	1	NM_001127392.3	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9 link	c.1285-29T>C	intron_variant	1		ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000675319.1 link	c.676-29T>C	intron_variant			ENSP00000502795.1	A0A6Q8PHM1
TMEM258	ENST00000535042.1 link	n.480-1880A>G	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63672

AN:

151660

Hom.:

14065

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.419

AC:

104830

AN:

250070

Hom.:

25203

AF XY:

0.397

AC XY:

53627

AN XY:

135212

show subpopulations

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 SAS exome

AF:

0.198

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.:

AF XY:

0.374

AC XY:

271611

AN XY:

725862

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.699

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.420

AC:

63787

AN:

151778

Hom.:

14121

Cov.:

AF XY:

0.421

AC XY:

31240

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.466

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.426

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.408

Hom.:

5107

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.81

CADD

Benign

1.6

DANN

Benign

0.60

BranchPoint Hunter

5.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over