rs174535

Variant names:

• chr11-61783884-T-C
• rs174535
• NM_001127392.3:c.3153T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-61783884-T-C
• chr11-61783884-T-G
• chr11-61783884-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001127392.3(MYRF):​c.3153T>C​(p.Ser1051Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,607,594 control chromosomes in the GnomAD database, including 102,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9107 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93760 hom.)
• Consequence: MYRF NM_001127392.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.41
• Publications: 153 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]

TMEM258 (HGNC:1164): (transmembrane protein 258) Involved in protein N-linked glycosylation. Located in endoplasmic reticulum. Part of oligosaccharyltransferase I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-61783884-T-C is Benign according to our data. Variant chr11-61783884-T-C is described in ClinVar as Benign. ClinVar VariationId is 1280429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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.3153T>C	p.Ser1051Ser	synonymous	Exon 24 of 27	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.3033T>C	p.Ser1011Ser	synonymous	Exon 23 of 26	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.3153T>C	p.Ser1051Ser	synonymous	Exon 24 of 27	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.3033T>C	p.Ser1011Ser	synonymous	Exon 23 of 26	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000539361.1	TSL:1	n.1698T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49302 AN: 151824 Hom.: 9084 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.380 AC: 91779 AN: 241624 AF XY: 0.362

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.678

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.563

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.348 AC: 507169 AN: 1455652 Hom.: 93760 Cov.: 45 AF XY: 0.342 AC XY: 247698 AN XY: 723512

African (AFR) AF: 0.176 AC: 5888 AN: 33408

American (AMR) AF: 0.662 AC: 29071 AN: 43906

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7435 AN: 25944

East Asian (EAS) AF: 0.462 AC: 18265 AN: 39570

South Asian (SAS) AF: 0.193 AC: 16433 AN: 85276

European-Finnish (FIN) AF: 0.424 AC: 22432 AN: 52858

Middle Eastern (MID) AF: 0.269 AC: 1532 AN: 5704

European-Non Finnish (NFE) AF: 0.347 AC: 384426 AN: 1108812

Other (OTH) AF: 0.360 AC: 21687 AN: 60174

GnomAD4 genome AF: 0.325 AC: 49341 AN: 151942 Hom.: 9107 Cov.: 32 AF XY: 0.329 AC XY: 24445 AN XY: 74278

African (AFR) AF: 0.193 AC: 7984 AN: 41430

American (AMR) AF: 0.506 AC: 7727 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2875 AN: 5150

South Asian (SAS) AF: 0.200 AC: 963 AN: 4810

European-Finnish (FIN) AF: 0.422 AC: 4464 AN: 10582

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23229 AN: 67910

Other (OTH) AF: 0.363 AC: 766 AN: 2108

Alfa AF: 0.337 Hom.: 40307

Bravo AF: 0.331

Asia WGS AF: 0.399 AC: 1387 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	-0.73
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs174535; hg19: chr11-61551356; COSMIC: COSV53888966; COSMIC: COSV53888966;