11-61766436-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001127392.3(MYRF):c.398+215T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 520,668 control chromosomes in the GnomAD database, including 39,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (10109 hom., cov: 32)
  • Exomes 𝑓: 0.37 (29660 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-61766436-T-C is Benign according to our data. Variant chr11-61766436-T-C is described in ClinVar as [Benign]. Clinvar id is 1245970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.398+215T>C		intron_variant		ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.398+215T>C		intron_variant		1	NM_001127392.3	P2
MYRF	ENST00000265460.9	c.371+215T>C		intron_variant		1		A2
MYRF	ENST00000675319.1	c.105+215T>C		intron_variant
MYRF	ENST00000537766.1	n.961T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50395 AN: 152004 Hom.: 10106 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.375 AC: 138170 AN: 368546 Hom.: 29660 Cov.: 4 AF XY: 0.371 AC XY: 70386 AN XY: 189674

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.331 AC: 50383 AN: 152122 Hom.: 10109 Cov.: 32 AF XY: 0.330 AC XY: 24513 AN XY: 74360

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.344

Alfa AF: 0.365 Hom.: 2299

Bravo AF: 0.311

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.38
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

LitVar

Other links and lift over

dbSNP: rs198467; hg19: chr11-61533908;