Genetic Variant MYRF:c.398+104A>T (chr11-61766325-A-T) – 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.398+104A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,293,288 control chromosomes in the GnomAD database, including 109,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10447 hom., cov: 32)

Exomes 𝑓: 0.40 ( 98984 hom. )

Consequence

MYRF
NM_001127392.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.690

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:

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=-0.85).

BP6

Variant 11-61766325-A-T is Benign according to our data. Variant chr11-61766325-A-T is described in ClinVar as [Benign]. Clinvar id is 1268050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.398+104A>T		intron_variant	Intron 3 of 26	ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYRF	ENST00000278836.10 link	c.398+104A>T	intron_variant	Intron 3 of 26	1	NM_001127392.3	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9 link	c.371+104A>T	intron_variant	Intron 3 of 25	1		ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000675319.1 link	c.104+104A>T	intron_variant	Intron 1 of 22			ENSP00000502795.1	A0A6Q8PHM1
MYRF	ENST00000537766.1 link	n.850A>T	non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52488

AN:

151780

Hom.:

10443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.403

AC:

460008

AN:

1141390

Hom.:

98984

Cov.:

AF XY:

0.398

AC XY:

222297

AN XY:

557946

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.526

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.346

AC:

52490

AN:

151898

Hom.:

10447

Cov.:

AF XY:

0.344

AC XY:

25571

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.482

Gnomad4 NFE

AF:

0.444

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.245

Hom.:

596

Bravo

AF:

0.327

Asia WGS

AF:

0.102

AC:

356

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

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.75

DANN

Benign

0.67

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