rs79255460

chr1-171636782-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000261.2(MYOC):c.731-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,537,068 control chromosomes in the GnomAD database, including 682 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 0.021 (56 hom., cov: 32)
  • Exomes 𝑓: 0.026 (626 hom.)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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]

MYOCOS (HGNC:53429): (myocilin opposite strand)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0206 (3142/152262) while in subpopulation NFE AF= 0.0299 (2037/68022). AF 95% confidence interval is 0.0289. There are 56 homozygotes in gnomad4. There are 1481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 56 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOC	NM_000261.2	c.731-73C>T		intron_variant		ENST00000037502.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOC	ENST00000037502.11	c.731-73C>T		intron_variant		1	NM_000261.2	P1
MYOCOS	ENST00000637303.1	c.235-1848G>A		intron_variant		5		A2
MYOC	ENST00000638471.1	c.*69-73C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3142 AN: 152144 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00923

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0264 AC: 36521 AN: 1384806 Hom.: 626 AF XY: 0.0265 AC XY: 18358 AN XY: 692444

Gnomad4 AFR exome AF: 0.00472

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0815

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0165

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0279

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0206 AC: 3142 AN: 152262 Hom.: 56 Cov.: 32 AF XY: 0.0199 AC XY: 1481 AN XY: 74454

Gnomad4 AFR AF: 0.00481

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00923

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0313 Hom.: 19

Bravo AF: 0.0207

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs79255460; hg19: chr1-171605922;