1-171649106-T-C

Variant names:

• chr1-171649106-T-C
• rs11586716
• NM_000261.2:c.604+2902A>G

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+2902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,016 control chromosomes in the GnomAD database, including 4,384 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 0.24 (4384 hom., cov: 32)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	NM_000261.2	MANE Select	c.604+2902A>G		intron	N/A	NP_000252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	ENST00000037502.11	TSL:1 MANE Select	c.604+2902A>G		intron	N/A	ENSP00000037502.5
	MYOC	ENST00000638471.1	TSL:5	n.130+3376A>G		intron	N/A	ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35800 AN: 151898 Hom.: 4388 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.236 AC: 35813 AN: 152016 Hom.: 4384 Cov.: 32 AF XY: 0.238 AC XY: 17714 AN XY: 74312

African (AFR) AF: 0.176 AC: 7302 AN: 41498

American (AMR) AF: 0.242 AC: 3701 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5182

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4814

European-Finnish (FIN) AF: 0.285 AC: 2991 AN: 10488

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17210 AN: 67986

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.234 Hom.: 624

Bravo AF: 0.223

Asia WGS AF: 0.303 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.82
PhyloP100		0.14
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: rs11586716; hg19: chr1-171618246;