1-171652694-C-T

Variant names:

• chr1-171652694-C-T
• rs2075648
• NM_000261.2:c.-83G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000261.2(MYOC):​c.-83G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,592,502 control chromosomes in the GnomAD database, including 18,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene MYOC is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.11 (1258 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16976 hom.)
• Consequence: MYOC NM_000261.2 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.12
• Publications: 30 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-171652694-C-T is Benign according to our data. Variant chr1-171652694-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 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.-83G>A		upstream_gene	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.-83G>A		upstream_gene	N/A	ENSP00000037502.5	Q99972
	MYOC	ENST00000971579.1		c.-83G>A		upstream_gene	N/A	ENSP00000641638.1
	MYOC	ENST00000877923.1		c.-83G>A		upstream_gene	N/A	ENSP00000547982.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16690 AN: 152016 Hom.: 1257 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.142 AC: 203981 AN: 1440368 Hom.: 16976 Cov.: 30 AF XY: 0.148 AC XY: 106237 AN XY: 715776

African (AFR) AF: 0.0313 AC: 1037 AN: 33134

American (AMR) AF: 0.102 AC: 4365 AN: 42596

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3417 AN: 25782

East Asian (EAS) AF: 0.0568 AC: 2236 AN: 39332

South Asian (SAS) AF: 0.342 AC: 28689 AN: 83900

European-Finnish (FIN) AF: 0.164 AC: 8050 AN: 49180

Middle Eastern (MID) AF: 0.145 AC: 610 AN: 4208

European-Non Finnish (NFE) AF: 0.134 AC: 147339 AN: 1102500

Other (OTH) AF: 0.138 AC: 8238 AN: 59736

GnomAD4 genome AF: 0.110 AC: 16700 AN: 152134 Hom.: 1258 Cov.: 32 AF XY: 0.114 AC XY: 8459 AN XY: 74360

African (AFR) AF: 0.0323 AC: 1341 AN: 41524

American (AMR) AF: 0.102 AC: 1559 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.0763 AC: 395 AN: 5180

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4812

European-Finnish (FIN) AF: 0.170 AC: 1791 AN: 10566

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9069 AN: 67972

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.123 Hom.: 1574

Bravo AF: 0.0958

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.76
PhyloP100		-2.1
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2075648; hg19: chr1-171621834; COSMIC: COSV50674517;