rs174536

Positions:

• chr11-61784455-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127392.3(MYRF):​c.3300+70A>C variant causes a intron 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 NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.358

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.3300+70A>C		intron_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.3300+70A>C		intron_variant		1	NM_001127392.3	ENSP00000278836.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44312 AN: 152050 Hom.: 8277 Cov.: 33

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.: 15 AF XY: 0.335 AC XY: 190931 AN XY: 570112

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.291 AC: 44344 AN: 152168 Hom.: 8300 Cov.: 33 AF XY: 0.297 AC XY: 22123 AN XY: 74394

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.341

Alfa AF: 0.319 Hom.: 3292

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.92
CADD	Benign	0.93
DANN	Benign	0.42

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: rs174536; hg19: chr11-61551927; COSMIC: COSV53892891; COSMIC: COSV53892891;