NM_000261.2:c.604+514T>A

Variant names:

• chr1-171651494-A-T
• rs235918
• NM_000261.2:c.604+514T>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+514T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,056 control chromosomes in the GnomAD database, including 42,153 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 0.74 (42153 hom., cov: 31)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• juvenile open angle glaucoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+514T>A		intron_variant	Intron 1 of 2	ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.604+514T>A		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+988T>A		intron_variant	Intron 1 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112823 AN: 151938 Hom.: 42110 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.743 AC: 112921 AN: 152056 Hom.: 42153 Cov.: 31 AF XY: 0.746 AC XY: 55450 AN XY: 74324

African (AFR) AF: 0.802 AC: 33269 AN: 41484

American (AMR) AF: 0.691 AC: 10557 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2711 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4549 AN: 5166

South Asian (SAS) AF: 0.810 AC: 3904 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7689 AN: 10554

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47797 AN: 67982

Other (OTH) AF: 0.749 AC: 1576 AN: 2104

Alfa AF: 0.727 Hom.: 4985

Bravo AF: 0.738

Asia WGS AF: 0.823 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs235918; hg19: chr1-171620634;