chr1-171642710-T-A

Variant names:

• chr1-171642710-T-A
• rs235870
• NM_000261.2:c.605-3988A>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.605-3988A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,630 control chromosomes in the GnomAD database, including 25,944 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. The gene MYOC is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.58 (25944 hom., cov: 29)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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: 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

Specifications for MYOC are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 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.605-3988A>T		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.605-3988A>T		intron	N/A	ENSP00000037502.5	Q99972
	MYOC	ENST00000971579.1		c.605-3988A>T		intron	N/A	ENSP00000641638.1
	MYOC	ENST00000877923.1		c.671-3988A>T		intron	N/A	ENSP00000547982.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88232 AN: 151512 Hom.: 25921 Cov.: 29

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.582 AC: 88315 AN: 151630 Hom.: 25944 Cov.: 29 AF XY: 0.584 AC XY: 43235 AN XY: 74040

African (AFR) AF: 0.625 AC: 25831 AN: 41324

American (AMR) AF: 0.538 AC: 8197 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3855 AN: 5154

South Asian (SAS) AF: 0.605 AC: 2898 AN: 4788

European-Finnish (FIN) AF: 0.573 AC: 6006 AN: 10478

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37997 AN: 67860

Other (OTH) AF: 0.560 AC: 1180 AN: 2106

Alfa AF: 0.564 Hom.: 3011

Bravo AF: 0.577

Asia WGS AF: 0.689 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-0.055
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: rs235870; hg19: chr1-171611850;