Variant rs509360 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 ENST00000278836.10(MYRF):c.2572+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,610,482 control chromosomes in the GnomAD database, including 334,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 24932 hom., cov: 32)

Exomes 𝑓: 0.64 ( 309699 hom. )

Consequence

MYRF
ENST00000278836.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.14

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

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-61781087-A-G is Benign according to our data. Variant chr11-61781087-A-G is described in ClinVar as [Benign]. Clinvar id is 1272274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3 linkuse as main transcript	c.2572+42A>G		intron_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10 linkuse as main transcript	c.2572+42A>G		intron_variant		1	NM_001127392.3	ENSP00000278836	P2	Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79640

AN:

151828

Hom.:

24916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.608

AC:

151310

AN:

248854

Hom.:

50782

AF XY:

0.596

AC XY:

80259

AN XY:

134700

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.834

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.571

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.663

GnomAD4 exome

AF:

0.638

AC:

930679

AN:

1458536

Hom.:

309699

Cov.:

AF XY:

0.628

AC XY:

455550

AN XY:

725740

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.715

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.650

Gnomad4 NFE exome

AF:

0.676

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.524

AC:

79671

AN:

151946

Hom.:

24932

Cov.:

AF XY:

0.524

AC XY:

38909

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.743

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.564

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.668

Gnomad4 OTH

AF:

0.604

Alfa

AF:

0.650

Hom.:

49318

Bravo

AF:

0.523

Asia WGS

AF:

0.462

AC:

1608

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	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.2

DANN

Benign

0.52

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