NM_000261.2:c.604+6465C>A

Variant names:

• chr1-171645543-G-T
• rs2236875
• NM_000261.2:c.604+6465C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000261.2(MYOC):​c.604+6465C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,220 control chromosomes in the GnomAD database, including 1,414 homozygotes. 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: 𝑓 0.13 (1414 hom., cov: 33)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 4 publications found

Genes affected

MYOC (HGNC:7610): (myocilin) MYOC encodes the protein myocilin, which is believed to have a role in cytoskeletal function. MYOC is expressed in many occular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. [provided by RefSeq, Jul 2008]

MYOC Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• juvenile open angle glaucoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• open-angle glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000261.2. 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
	MYOC	NM_000261.2	MANE Select	c.604+6465C>A		intron	N/A	NP_000252.1	Q99972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	ENST00000037502.11	TSL:1 MANE Select	c.604+6465C>A		intron	N/A	ENSP00000037502.5	Q99972
	MYOC	ENST00000971579.1		c.604+6465C>A		intron	N/A	ENSP00000641638.1
	MYOC	ENST00000877923.1		c.670+5827C>A		intron	N/A	ENSP00000547982.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19554 AN: 152102 Hom.: 1406 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19594 AN: 152220 Hom.: 1414 Cov.: 33 AF XY: 0.130 AC XY: 9653 AN XY: 74420

African (AFR) AF: 0.195 AC: 8087 AN: 41518

American (AMR) AF: 0.118 AC: 1812 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5168

South Asian (SAS) AF: 0.0884 AC: 427 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1210 AN: 10598

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6247 AN: 68022

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.102 Hom.: 3506

Bravo AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		0.097
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: rs2236875; hg19: chr1-171614683;