rs235875

Variant names:

• chr1-171644616-C-T
• rs235875
• NM_000261.2:c.605-5894G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000261.2(MYOC):​c.605-5894G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 141,240 control chromosomes in the GnomAD database, including 2,399 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 0.17 (2399 hom., cov: 29)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.605-5894G>A		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.605-5894G>A		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.131-1225G>A		intron_variant	Intron 1 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 23696 AN: 141170 Hom.: 2399 Cov.: 29

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.168 AC: 23690 AN: 141240 Hom.: 2399 Cov.: 29 AF XY: 0.169 AC XY: 11477 AN XY: 68088

African (AFR) AF: 0.0427 AC: 1623 AN: 38034

American (AMR) AF: 0.172 AC: 2345 AN: 13598

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 740 AN: 3396

East Asian (EAS) AF: 0.326 AC: 1625 AN: 4988

South Asian (SAS) AF: 0.118 AC: 530 AN: 4508

European-Finnish (FIN) AF: 0.226 AC: 1883 AN: 8334

Middle Eastern (MID) AF: 0.198 AC: 50 AN: 252

European-Non Finnish (NFE) AF: 0.220 AC: 14353 AN: 65300

Other (OTH) AF: 0.182 AC: 355 AN: 1948

Alfa AF: 0.187 Hom.: 3890

Bravo AF: 0.151

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		0.026
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: rs235875; hg19: chr1-171613756;