dbSNP rs2956395: MYRF-AS1:n.533-2772G>C (chr11-61752514-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000536405.6(MYRF-AS1):n.533-2772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 149,460 control chromosomes in the GnomAD database, including 5,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5686 hom., cov: 32)

Exomes 𝑓: 0.32 ( 57 hom. )

Consequence

MYRF-AS1
ENST00000536405.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.58

Publications

6 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-61752514-C-G is Benign according to our data. Variant chr11-61752514-C-G is described in ClinVar as Benign. ClinVar VariationId is 1248440.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536405.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	NM_001127392.3	MANE Select	c.-231C>G		upstream_gene	N/A	NP_001120864.1	Q9Y2G1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MYRF-AS1	ENST00000536405.6	TSL:1	n.533-2772G>C	intron	N/A
MYRF-AS1	ENST00000541891.2	TSL:3	n.96-2772G>C	intron	N/A
MYRF-AS1	ENST00000833478.1		n.300-2772G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

36639

AN:

148190

Hom.:

5689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0697

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.349

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.322

AC:

375

AN:

1166

Hom.:

AF XY:

0.325

AC XY:

197

AN XY:

606

show subpopulations

African (AFR)

AF:

0.0556

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.318

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.323

AC:

332

AN:

1028

Other (OTH)

AF:

0.426

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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

100

<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:

0.247

AC:

36619

AN:

148294

Hom.:

5686

Cov.:

AF XY:

0.248

AC XY:

17884

AN XY:

72250

show subpopulations

African (AFR)

AF:

0.0695

AC:

2859

AN:

41118

American (AMR)

AF:

0.240

AC:

3583

AN:

14918

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1623

AN:

3416

East Asian (EAS)

AF:

0.122

AC:

619

AN:

5088

South Asian (SAS)

AF:

0.236

AC:

1138

AN:

4812

European-Finnish (FIN)

AF:

0.337

AC:

3043

AN:

9040

Middle Eastern (MID)

AF:

0.344

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.342

AC:

22811

AN:

66626

Other (OTH)

AF:

0.273

AC:

566

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1368

2736

4103

5471

6839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.172

Hom.:

388

Bravo

AF:

0.236

Asia WGS

AF:

0.155

AC:

527

AN:

3394

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

(source)

DANN

Benign

0.43

PhyloP100

-1.6

PromoterAI

-0.075

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over