rs2901559

Variant names:

• chr1-171651350-C-A
• rs2901559
• NM_000261.2:c.604+658G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-171651350-C-A
• chr1-171651350-C-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+658G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 146,928 control chromosomes in the GnomAD database, including 50,565 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 0.83 (50565 hom., cov: 22)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.66
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+658G>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+658G>T		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+1132G>T		intron_variant	Intron 1 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 121195 AN: 146814 Hom.: 50501 Cov.: 22

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.826 AC: 121313 AN: 146928 Hom.: 50565 Cov.: 22 AF XY: 0.829 AC XY: 59086 AN XY: 71234

African (AFR) AF: 0.936 AC: 37334 AN: 39902

American (AMR) AF: 0.795 AC: 11573 AN: 14560

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3090 AN: 3434

East Asian (EAS) AF: 0.884 AC: 4306 AN: 4872

South Asian (SAS) AF: 0.840 AC: 3815 AN: 4544

European-Finnish (FIN) AF: 0.788 AC: 7606 AN: 9648

Middle Eastern (MID) AF: 0.840 AC: 242 AN: 288

European-Non Finnish (NFE) AF: 0.764 AC: 51017 AN: 66754

Other (OTH) AF: 0.826 AC: 1691 AN: 2046

Alfa AF: 0.790 Hom.: 60315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.063
DANN	Benign	0.38
PhyloP100		-3.7
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: rs2901559; hg19: chr1-171620490;