rs372575659

Variant names:

• chr11-61765707-C-T
• rs372575659
• NM_001127392.3:c.129C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001127392.3(MYRF):​c.129C>T​(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,611,794 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00065 (2 hom.)
• Consequence: MYRF NM_001127392.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.67
• Publications: 0 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 Gene-Disease associations (from GenCC):

• cardiac-urogenital syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hyperopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• encephalitis/encephalopathy, mild, with reversible myelin vacuolization

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-61765707-C-T is Benign according to our data. Variant chr11-61765707-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3057910.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.67 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000236 (36/152236) while in subpopulation NFE AF = 0.000279 (19/68000). AF 95% confidence interval is 0.000182. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 36 AD,Unknown gene.

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.129C>T	p.Ser43Ser	synonymous	Exon 2 of 27	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.102C>T	p.Ser34Ser	synonymous	Exon 2 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.129C>T	p.Ser43Ser	synonymous	Exon 2 of 27	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.102C>T	p.Ser34Ser	synonymous	Exon 2 of 26	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 27	ENSP00000526870.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000226 AC: 56 AN: 247420 AF XY: 0.000246

Gnomad AFR exome AF: 0.000254

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000341

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000654 AC: 955 AN: 1459558 Hom.: 2 Cov.: 31 AF XY: 0.000601 AC XY: 436 AN XY: 726044

African (AFR) AF: 0.000120 AC: 4 AN: 33432

American (AMR) AF: 0.000314 AC: 14 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86054

European-Finnish (FIN) AF: 0.0000571 AC: 3 AN: 52556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5366

European-Non Finnish (NFE) AF: 0.000821 AC: 912 AN: 1111484

Other (OTH) AF: 0.000348 AC: 21 AN: 60282

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74436

African (AFR) AF: 0.000265 AC: 11 AN: 41536

American (AMR) AF: 0.000261 AC: 4 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.000246

EpiCase AF: 0.000382

EpiControl AF: 0.000595

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYRF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.26
DANN	Benign	0.90
PhyloP100		-2.7
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs372575659; hg19: chr11-61533179; COSMIC: COSV53889287; COSMIC: COSV53889287;