chr11-61766325-A-C

Variant names:

• chr11-61766325-A-C
• rs4963418
• NM_001127392.3:c.398+104A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127392.3(MYRF):​c.398+104A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000874 in 1,143,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.398+104A>C		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.371+104A>C		intron	N/A	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.398+104A>C		intron	N/A	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.371+104A>C		intron	N/A	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.398+104A>C		intron	N/A	ENSP00000526870.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.74e-7 AC: 1 AN: 1143684 Hom.: 0 Cov.: 15 AF XY: 0.00000179 AC XY: 1 AN XY: 559078

African (AFR) AF: 0.0000390 AC: 1 AN: 25622

American (AMR) AF: 0.00 AC: 0 AN: 19520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17770

East Asian (EAS) AF: 0.00 AC: 0 AN: 34072

South Asian (SAS) AF: 0.00 AC: 0 AN: 57184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 902176

Other (OTH) AF: 0.00 AC: 0 AN: 48376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.59
PhyloP100		-0.69
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4963418; hg19: chr11-61533797;