rs198464

Positions:

• chr11-61754149-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127392.3(MYRF):​c.46+1359G>A variant causes a intron 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 NM_001127392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYRF	NM_001127392.3	c.46+1359G>A		intron_variant		ENST00000278836.10
MYRF-AS1	NR_026882.1	n.816C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.46+1359G>A		intron_variant		1	NM_001127392.3	P2
MYRF-AS1	ENST00000244906.6	n.807C>T		non_coding_transcript_exon_variant	4/4	1
MYRF-AS1	ENST00000536405.5	n.504+1486C>T		intron_variant, non_coding_transcript_variant		1
MYRF	ENST00000537766.1	n.149+1359G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67914 AN: 151942 Hom.: 15604 Cov.: 32

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: 90 AN: 182 Hom.: 27 Cov.: 0 AF XY: 0.569 AC XY: 58 AN XY: 102

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.447 AC: 67946 AN: 152060 Hom.: 15609 Cov.: 32 AF XY: 0.446 AC XY: 33191 AN XY: 74340

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.454

Alfa AF: 0.482 Hom.: 25120

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
DANN	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs198464; hg19: chr11-61521621;