Variant 11-61781986-A-G 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.3016+162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 807,536 control chromosomes in the GnomAD database, including 49,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8100 hom., cov: 34)

Exomes 𝑓: 0.34 ( 40992 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.46

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-61781986-A-G is Benign according to our data. Variant chr11-61781986-A-G is described in ClinVar as [Benign]. Clinvar id is 1227305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.3016+162A>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.3016+162A>G		intron_variant		1	NM_001127392.3	ENSP00000278836	P2	Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43386

AN:

152134

Hom.:

8077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0776

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.341

AC:

223645

AN:

655284

Hom.:

40992

Cov.:

AF XY:

0.336

AC XY:

110561

AN XY:

328606

show subpopulations

Gnomad4 AFR exome

AF:

0.0652

Gnomad4 AMR exome

AF:

0.596

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.285

AC:

43418

AN:

152252

Hom.:

8100

Cov.:

AF XY:

0.287

AC XY:

21368

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0774

Gnomad4 AMR

AF:

0.499

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.554

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.346

Alfa

AF:

0.323

Hom.:

5139

Bravo

AF:

0.294

Asia WGS

AF:

0.362

AC:

1258

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

-0.87

CADD

Benign

0.038

DANN

Benign

0.36

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