dbSNP rs174536: MYRF:n.2269A>C (chr11-61784455-A-C) – 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 ENST00000539361.1(MYRF):n.2269A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,275,984 control chromosomes in the GnomAD database, including 79,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8300 hom., cov: 33)

Exomes 𝑓: 0.34 ( 70884 hom. )

Consequence

MYRF
ENST00000539361.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.358

Publications

82 publications found

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=-0.92).

BP6

Variant 11-61784455-A-C is Benign according to our data. Variant chr11-61784455-A-C is described in ClinVar as Benign. ClinVar VariationId is 1259171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.3300+70A>C		intron_variant	Intron 25 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.3300+70A>C		intron_variant	Intron 25 of 26	1	NM_001127392.3	ENSP00000278836.4		Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44312

AN:

152050

Hom.:

8277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.337

GnomAD4 exome

AF:

0.341

AC:

383582

AN:

1123816

Hom.:

70884

Cov.:

AF XY:

0.335

AC XY:

190931

AN XY:

570112

show subpopulations

African (AFR)

AF:

0.0706

AC:

1878

AN:

26592

American (AMR)

AF:

0.641

AC:

23278

AN:

36336

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

6475

AN:

23124

East Asian (EAS)

AF:

0.453

AC:

16580

AN:

36608

South Asian (SAS)

AF:

0.194

AC:

14807

AN:

76336

European-Finnish (FIN)

AF:

0.424

AC:

18641

AN:

43968

Middle Eastern (MID)

AF:

0.258

AC:

1207

AN:

4672

European-Non Finnish (NFE)

AF:

0.343

AC:

283548

AN:

827174

Other (OTH)

AF:

0.350

AC:

17168

AN:

49006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12079

24157

36236

48314

60393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8110

16220

24330

32440

40550

<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:

0.291

AC:

44344

AN:

152168

Hom.:

8300

Cov.:

AF XY:

0.297

AC XY:

22123

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0834

AC:

3466

AN:

41558

American (AMR)

AF:

0.490

AC:

7487

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

997

AN:

3468

East Asian (EAS)

AF:

0.555

AC:

2864

AN:

5158

South Asian (SAS)

AF:

0.201

AC:

971

AN:

4824

European-Finnish (FIN)

AF:

0.420

AC:

4455

AN:

10598

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23069

AN:

67956

Other (OTH)

AF:

0.341

AC:

720

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1496

2991

4487

5982

7478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.324

Hom.:

20004

Bravo

AF:

0.292

Asia WGS

AF:

0.394

AC:

1369

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

-0.92

CADD

Benign

0.93

(source)

DANN

Benign

0.42

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over