rs2901558

Variant names:

• chr1-171651348-C-A
• rs2901558
• NM_000261.2:c.604+660G>T

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+660G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 146,056 control chromosomes in the GnomAD database, including 31,307 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 0.64 (31307 hom., cov: 21)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+660G>T		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+660G>T		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+1134G>T		intron_variant	Intron 1 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 92917 AN: 145946 Hom.: 31258 Cov.: 21

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.637 AC: 93024 AN: 146056 Hom.: 31307 Cov.: 21 AF XY: 0.643 AC XY: 45436 AN XY: 70702

African (AFR) AF: 0.851 AC: 33793 AN: 39706

American (AMR) AF: 0.613 AC: 8854 AN: 14448

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2114 AN: 3416

East Asian (EAS) AF: 0.601 AC: 2901 AN: 4824

South Asian (SAS) AF: 0.708 AC: 3162 AN: 4466

European-Finnish (FIN) AF: 0.582 AC: 5478 AN: 9418

Middle Eastern (MID) AF: 0.625 AC: 180 AN: 288

European-Non Finnish (NFE) AF: 0.523 AC: 34847 AN: 66580

Other (OTH) AF: 0.636 AC: 1290 AN: 2028

Alfa AF: 0.709 Hom.: 3519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.43
PhyloP100		-0.86
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: rs2901558; hg19: chr1-171620488;