11-61752514-C-G

Variant names:

• chr11-61752514-C-G
• rs2956395
• ENST00000536405.5:n.505-2772G>C

Variant summary

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

The ENST00000536405.5(MYRF-AS1):​n.505-2772G>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 ENST00000536405.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

Genes affected

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

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 11-61752514-C-G is Benign according to our data. Variant chr11-61752514-C-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.-231C>G		upstream_gene_variant		ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF-AS1	ENST00000536405.5	n.505-2772G>C		intron_variant	Intron 3 of 5	1
MYRF	ENST00000278836.10	c.-231C>G		upstream_gene_variant		1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000537766.1	n.-128C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 36639 AN: 148190 Hom.: 5689 Cov.: 32

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.: 57 AF XY: 0.325 AC XY: 197 AN XY: 606

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.247 AC: 36619 AN: 148294 Hom.: 5686 Cov.: 32 AF XY: 0.248 AC XY: 17884 AN XY: 72250

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.273

Alfa AF: 0.172 Hom.: 388

Bravo AF: 0.236

Asia WGS AF: 0.155 AC: 527 AN: 3394

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2956395; hg19: chr11-61519986;