dbSNP rs174532: MYRF:c.2764+73G>A (chr11-61781402-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001127392.3(MYRF):c.2764+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,571,074 control chromosomes in the GnomAD database, including 58,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4099 hom., cov: 33)

Exomes 𝑓: 0.26 ( 54005 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.590

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=-0.82).

BP6

Variant 11-61781402-G-A is Benign according to our data. Variant chr11-61781402-G-A is described in ClinVar as [Benign]. Clinvar id is 1257534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.2764+73G>A		intron_variant	Intron 21 of 26	ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10 link	c.2764+73G>A		intron_variant	Intron 21 of 26	1	NM_001127392.3	ENSP00000278836.4		Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30325

AN:

152108

Hom.:

4099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.227

GnomAD4 exome

AF:

0.261

AC:

370919

AN:

1418848

Hom.:

54005

Cov.:

AF XY:

0.256

AC XY:

179717

AN XY:

702446

show subpopulations

Gnomad4 AFR exome

AF:

0.0466

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.000459

Gnomad4 SAS exome

AF:

0.0554

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.199

AC:

30317

AN:

152226

Hom.:

4099

Cov.:

AF XY:

0.194

AC XY:

14419

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0540

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0453

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.285

Hom.:

8833

Bravo

AF:

0.195

Asia WGS

AF:

0.0400

AC:

143

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

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

DANN

Benign

0.62

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