dbSNP rs198464: MYRF-AS1:n.823C>T (chr11-61754149-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000244906.7(MYRF-AS1):n.823C>T 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 0.447 in 152,242 control chromosomes in the GnomAD database, including 15,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 15609 hom., cov: 32)

Exomes 𝑓: 0.49 ( 27 hom. )

Consequence

MYRF-AS1
ENST00000244906.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

29 publications found

Variant links:

Genes affected

MYRF-AS1 (HGNC:24506): (MYRF antisense RNA 1)

MYRF-AS1 links:

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 Gene-Disease associations (from GenCC):

cardiac-urogenital syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
hyperopia
Inheritance: AD Classification: STRONG Submitted by: G2P
encephalitis/encephalopathy, mild, with reversible myelin vacuolization
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MYRF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.46+1359G>A		intron_variant	Intron 1 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.46+1359G>A		intron_variant	Intron 1 of 26	1	NM_001127392.3	ENSP00000278836.4		Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67914

AN:

151942

Hom.:

15604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.457

GnomAD4 exome

AF:

0.495

AC:

AN:

182

Hom.:

Cov.:

AF XY:

0.569

AC XY:

AN XY:

102

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.471

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.643

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.447

AC:

67946

AN:

152060

Hom.:

15609

Cov.:

AF XY:

0.446

AC XY:

33191

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.397

AC:

16469

AN:

41474

American (AMR)

AF:

0.349

AC:

5332

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2122

AN:

3472

East Asian (EAS)

AF:

0.400

AC:

2063

AN:

5160

South Asian (SAS)

AF:

0.367

AC:

1769

AN:

4826

European-Finnish (FIN)

AF:

0.525

AC:

5550

AN:

10576

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.488

AC:

33157

AN:

67952

Other (OTH)

AF:

0.454

AC:

960

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1968

3937

5905

7874

9842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.468

Hom.:

41681

Bravo

AF:

0.438

Asia WGS

AF:

0.355

AC:

1234

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.4

(source)

DANN

Benign

0.32

PhyloP100

0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over