rs2286008

Variant names:

• chr11-61755487-G-T
• rs2286008
• NM_001127392.3:c.46+2697G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-61755487-G-T
• chr11-61755487-G-A
• chr11-61755487-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127392.3(MYRF):​c.46+2697G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,600,060 control chromosomes in the GnomAD database, including 815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0097 (722 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.956
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-61755487-G-T is Benign according to our data. Variant chr11-61755487-G-T is described in ClinVar as Benign. ClinVar VariationId is 1246473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127392.3. 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.46+2697G>T		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.19+45G>T		intron	N/A	NP_037411.1	Q9Y2G1-2
	MYRF-AS1	NR_026882.1		n.519+148C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.46+2697G>T		intron	N/A	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.19+45G>T		intron	N/A	ENSP00000265460.5	Q9Y2G1-2
	MYRF-AS1	ENST00000244906.7	TSL:1	n.526+148C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2717 AN: 152140 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.0215 AC: 5130 AN: 238196 AF XY: 0.0234

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.000953

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000472

Gnomad OTH exome AF: 0.00887

GnomAD4 exome AF: 0.00973 AC: 14092 AN: 1447802 Hom.: 722 Cov.: 29 AF XY: 0.0113 AC XY: 8166 AN XY: 720630

African (AFR) AF: 0.0340 AC: 1124 AN: 33038

American (AMR) AF: 0.00375 AC: 161 AN: 42944

Ashkenazi Jewish (ASJ) AF: 0.00136 AC: 35 AN: 25722

East Asian (EAS) AF: 0.139 AC: 5512 AN: 39566

South Asian (SAS) AF: 0.0693 AC: 5896 AN: 85104

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52102

Middle Eastern (MID) AF: 0.00369 AC: 21 AN: 5696

European-Non Finnish (NFE) AF: 0.000265 AC: 292 AN: 1103856

Other (OTH) AF: 0.0176 AC: 1050 AN: 59774

GnomAD4 genome AF: 0.0179 AC: 2719 AN: 152258 Hom.: 93 Cov.: 33 AF XY: 0.0191 AC XY: 1419 AN XY: 74448

African (AFR) AF: 0.0367 AC: 1526 AN: 41550

American (AMR) AF: 0.00640 AC: 98 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5166

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4820

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68000

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.00437 Hom.: 12

Bravo AF: 0.0169

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		0.96
PromoterAI		-0.0015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2286008; hg19: chr11-61522959;