dbSNP rs108499: MYRF:c.2248-77C>T (chr11-61779765-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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:

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.2248-77C>T		intron_variant	Intron 16 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.2248-77C>T		intron_variant	Intron 16 of 26	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

AC:

1689

AN:

29378

Gnomad4 AMR exome

AF:

0.642

AC:

24354

AN:

37914

Gnomad4 ASJ exome

AF:

0.237

AC:

5519

AN:

23298

Gnomad4 EAS exome

AF:

0.452

AC:

16538

AN:

36624

Gnomad4 SAS exome

AF:

0.156

AC:

11960

AN:

76668

Gnomad4 FIN exome

AF:

0.349

AC:

17723

AN:

50710

Gnomad4 NFE exome

AF:

0.334

AC:

317621

AN:

950650

Gnomad4 Remaining exome

AF:

0.333

AC:

17653

AN:

53090

Heterozygous variant carriers

13776

27552

41327

55103

68879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

10040

20080

30120

40160

50200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.0747495

AN:

0.0747495

Gnomad4 AMR

AF:

0.482

AC:

0.482215

AN:

0.482215

Gnomad4 ASJ

AF:

0.244

AC:

0.243516

AN:

0.243516

Gnomad4 EAS

AF:

0.549

AC:

0.549342

AN:

0.549342

Gnomad4 SAS

AF:

0.162

AC:

0.161893

AN:

0.161893

Gnomad4 FIN

AF:

0.341

AC:

0.340823

AN:

0.340823

Gnomad4 NFE

AF:

0.325

AC:

0.324929

AN:

0.324929

Gnomad4 OTH

AF:

0.335

AC:

0.335227

AN:

0.335227

Heterozygous variant carriers

1397

2794

4192

5589

6986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.320

Hom.:

24023

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

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

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

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