Variant rs108499 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.2248-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,415,824 control chromosomes in the GnomAD database, including 81,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 7527 hom., cov: 33)

Exomes 𝑓: 0.33 ( 73991 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.775

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:

MYRF (HGNC:):

MYRF 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=-0.82).

BP6

Variant 11-61779765-C-T is Benign according to our data. Variant chr11-61779765-C-T is described in ClinVar as [Benign]. Clinvar id is 1236921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 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.2248-77C>T		intron_variant		ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10 linkuse as main transcript	c.2248-77C>T		intron_variant		1	NM_001127392.3	ENSP00000278836.4		Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41597

AN:

152028

Hom.:

7504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.328

AC:

414262

AN:

1263678

Hom.:

73991

Cov.:

AF XY:

0.321

AC XY:

201626

AN XY:

627816

show subpopulations

Gnomad4 AFR exome

AF:

0.0575

Gnomad4 AMR exome

AF:

0.642

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.452

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.274

AC:

41631

AN:

152146

Hom.:

7527

Cov.:

AF XY:

0.276

AC XY:

20519

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0747

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.549

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.319

Hom.:

9113

Bravo

AF:

0.283

Asia WGS

AF:

0.352

AC:

1222

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

-0.82

CADD

Benign

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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