11-61766325-A-T

Variant names:

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

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.398+104A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,293,288 control chromosomes in the GnomAD database, including 109,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10447 hom., cov: 32)
  • Exomes 𝑓: 0.40 (98984 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-61766325-A-T is Benign according to our data. Variant chr11-61766325-A-T is described in ClinVar as Benign. ClinVar VariationId is 1268050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 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.398+104A>T		intron	N/A	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.371+104A>T		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>T		intron	N/A	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.371+104A>T		intron	N/A	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.398+104A>T		intron	N/A	ENSP00000526870.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52488 AN: 151780 Hom.: 10443 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.403 AC: 460008 AN: 1141390 Hom.: 98984 Cov.: 15 AF XY: 0.398 AC XY: 222297 AN XY: 557946

African (AFR) AF: 0.202 AC: 5173 AN: 25590

American (AMR) AF: 0.260 AC: 5075 AN: 19508

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 9328 AN: 17748

East Asian (EAS) AF: 0.0109 AC: 371 AN: 34062

South Asian (SAS) AF: 0.174 AC: 9943 AN: 57102

European-Finnish (FIN) AF: 0.485 AC: 17042 AN: 35160

Middle Eastern (MID) AF: 0.462 AC: 1738 AN: 3760

European-Non Finnish (NFE) AF: 0.437 AC: 392947 AN: 900144

Other (OTH) AF: 0.381 AC: 18391 AN: 48316

GnomAD4 genome AF: 0.346 AC: 52490 AN: 151898 Hom.: 10447 Cov.: 32 AF XY: 0.344 AC XY: 25571 AN XY: 74276

African (AFR) AF: 0.204 AC: 8461 AN: 41432

American (AMR) AF: 0.311 AC: 4748 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3470

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5162

South Asian (SAS) AF: 0.148 AC: 712 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5094 AN: 10562

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30129 AN: 67880

Other (OTH) AF: 0.355 AC: 750 AN: 2110

Alfa AF: 0.245 Hom.: 596

Bravo AF: 0.327

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	0.75
DANN	Benign	0.67
PhyloP100		-0.69
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;