Variant chr11-61769111-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001127392.3(MYRF):c.399-149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 585,250 control chromosomes in the GnomAD database, including 112,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 26879 hom., cov: 34)

Exomes 𝑓: 0.61 ( 85883 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00400

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-61769111-G-A is Benign according to our data. Variant chr11-61769111-G-A is described in ClinVar as [Benign]. Clinvar id is 1230875.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3 linkuse as main transcript	c.399-149G>A		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10 linkuse as main transcript	c.399-149G>A	intron_variant	1	NM_001127392.3	P2	Q9Y2G1-1
MYRF	ENST00000265460.9 linkuse as main transcript	c.372-149G>A	intron_variant	1		A2	Q9Y2G1-2
MYRF	ENST00000675319.1 linkuse as main transcript	c.106-2389G>A	intron_variant
TMEM258	ENST00000535042.1 linkuse as main transcript	n.649-338C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

89041

AN:

151974

Hom.:

26860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.596

GnomAD4 exome

AF:

0.614

AC:

266136

AN:

433158

Hom.:

85883

AF XY:

0.625

AC XY:

142018

AN XY:

227216

show subpopulations

Gnomad4 AFR exome

AF:

0.552

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.469

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.586

AC:

89087

AN:

152092

Hom.:

26879

Cov.:

AF XY:

0.590

AC XY:

43828

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.562

Gnomad4 AMR

AF:

0.658

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.986

Gnomad4 SAS

AF:

0.849

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.575

Hom.:

10911

Bravo

AF:

0.595

Asia WGS

AF:

0.878

AC:

3054

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.82

CADD

Benign

7.2

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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